WO2024264012A1 - Bioavailability enhancing ionic liquid formulations including anthelminitic benzimidazole compounds and uses thereof - Google Patents

Abstract

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of oral bioavailability enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds. In particular, the present disclosure provides methods for treating or preventing infectious diseases with one or more oral bioavailability enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds, or pharmaceutically acceptable salts thereof, or compositions comprising the same and an additional anti-fungal agent, and pharmaceutical compositions comprising one or more oral bioavailability enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds and at least one additional anti-fungal agent.

Description

Attorney Docket No. UAZ-43145.601 UA23-030 BIOAVAILABILITY ENHANCING IONIC LIQUID FORMULATIONS INCLUDING ANTHELMINITIC BENZIMIDAZOLE COMPOUNDS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS The present application claims priority to U.S. Provisional Application No.63/509,745, filed June 22, 2023, which is incorporated herein by reference in its entirety. FIELD OF THE INVENTION This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of bioavailability (e.g., oral and local bioavailability) enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds. In particular, the present disclosure provides methods for treating or preventing infectious diseases with one or more oral bioavailability enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds, or pharmaceutically acceptable salts thereof, or compositions comprising the same and an additional anti-fungal agent, and pharmaceutical compositions comprising one or more oral bioavailability enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds and at least one additional anti-fungal agent. INTRODUCTION Cryptococcal meningitis (CM) is a deadly fungal infection due to Cryptococcus neoformans that predominantly causes disease in immunocompromised individuals. Globally, CM affects ~ 220,000 individuals every year and is the second leading cause of death in HIV/AIDS patients. The first-line amphotericin B (AmB)-flucytosine (5-FC) combination CM therapy has several limitations such as a lack of oral dosing for AmB, high cost, AmB-associated toxicity, 5-FC associated hematologic toxicity, and scarcity of combination therapy in many areas of the world. Therefore, there is a dire need for new CM therapeutics. ) is an FDA- approved

CNS penetrability, and minimal first-pass metabolism when compared to other anthelmintic Attorney Docket No. UAZ-43145.601 UA23-030 benzimidazoles. OXF is currently recommended for the treatment of porcine neurocysticercosis, a parasitic infection of the CNS, and is being evaluated in a clinical trial for the treatment of human neurocysticercosis due to its safety at an oral dose of 60 mg/kg in humans. Preliminary data indicates that OXF is active against laboratory and clinical strains of C. neoformans in vitro (IC90: 2.5-5 µM). Unlike hitherto explored anthelmintic benzimidazoles, treatment with daily oral 15-25 mg/kg OXF suspension in a mouse CM model showed 1-2 log reductions in fungal burden in lungs and brain that resulted in improved mouse survival. However, due to high crystallinity, hydrophobicity, and poor water and lipid solubility, OXF does not show dose- proportional preclinical efficacy and clinical pharmacokinetics. Hence, the development of strategies that can improve oral bioavailability, and dose proportionality of OXF are needed to facilitate its repurposing for oral CM therapy. The present invention addresses this need. SUMMARY OF THE INVENTION Ionic liquids (ILs) are organic salts with a melting point of < 150°C that can be liquid at room temperature, depending upon the cations and anions involved in the formation. An emerging strategy to enhance solubility and bioavailability (e.g., oral and local bioavailability) is the transformation of hydrophobic ionizable drugs into ILs using Generally Regarded As Safe (GRAS) counterions. Experiments conducted during the course of developing embodiments for the present invention determined that the transformation of OXF and other anthelmintic benzimidazoles into amphiphilic ILs using the FDA-approved fatty anion docusate sodium led to the abolishment of crystallinity, significant improvement in lipid solubility and in vitro antifungal efficacy. Such experiments demonstrated that these docusate-based ILs can be efficiently packaged in nanomicelles of SoluPlus, an amphiphilic biodegradable polymer capable of oral bioavailability enhancement. Transformation of OXF into ILs (OXF-ILs), by harnessing the electrostatic interaction between OXF and GRAS anions, and subsequent incorporation of OXF ILs into SoluPlus nanomicelles or lipid nanoemulsion was shown to improve the oral bioavailability and in vivo efficacy in a murine CM model. Accordingly, the present invention relates to a new class of oral bioavailability enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds. In particular, the present disclosure provides methods for treating or preventing infectious diseases with one or more oral bioavailability enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds, or pharmaceutically acceptable salts thereof, or compositions Attorney Docket No. UAZ-43145.601 UA23-030 comprising the same and an additional anti-fungal agent, and pharmaceutical compositions comprising one or more oral bioavailability enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds and at least one additional anti-fungal agent. In certain embodiments, the present invention provides a composition comprising an ionic liquid formulation comprising: a) a protonated compound encompassed within the following (Formula I); and b) an anionic

R1, R2, and the anionic component chemical

render the formulation a liquid at room temperature; wherein R1, R2, and the anionic component chemical moieties that render the formulation with a melting point less than 100 degree C; wherein R1, R2, and the anionic component chemical moieties that render the formulation as an amphiphilic liquid; wherein R1, R2, and the anionic component chemical moieties that render the formulation a non-crystalline form; wherein R1, R2, and the anionic component chemical moieties that render the formulation as therapeutically effective agent for treating a condition or disease known to be treatable with OXF; wherein R1, R2, and the anionic component chemical moieties that render the formulation as having therapeutically effective antifungal activity; wherein R1, R2, and the anionic component chemical moieties that render the formulation as having therapeutically effective antifungal activity against Cryptococcus neoformans; wherein R1, R2, and the anionic component chemical moieties that render the formulation as therapeutically effective agent for perturbing microtubule assembly in Cryptococcus neoformans; wherein R1, R2, and the anionic component chemical moieties that render the formulation as therapeutically effective agent for treating fungal disorders; wherein R1, R2, and the anionic component chemical moieties that render the formulation as therapeutically effective agent for treating Cryptococcal meningitis (CM); wherein R1, R2, and the anionic component chemical moieties that render the formulation as therapeutically effective agent for treating human neurocysticercosis wherein R1, R2, and the anionic component chemical moieties that render the formulation as having enhanced bioavailability of the compound encompassed within Formula I; wherein R1, R2, and the anionic component chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated Attorney Docket No. UAZ-43145.601 UA23-030 within) with biodegradable polymers; wherein R1, R2, and the anionic component chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated within) with biodegradable polymers thereby enhancing bioavailabity of the ionic liquid formulation; wherein R1, R2, and the anionic component chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated within) with lipid nanoemulsions; and wherein R1, R2, and the anionic component chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated within) with nanomicelles (e.g., SoluPlus nanomicelles) (e.g., lipid nanoemulsions). O In some (substituted or unsubstituted). In some embodiments, R2 is C6) alkyl (e.g., CH3

). In some embodiments, the anionic component is selected from an anionic therapeutic agent, an anionic amino acid, an anionic nutraceutical, an anionic agrochemical molecule, an anionic functional food, an anionic excipient, and a pharmaceutically acceptable anion. In some embodiments, the anionic component is an anionic carboxylate, an anionic sulfonate, an anionic sulfate, an anionic phosphate, an anionic phosphonate, an anionic sulfamate, or a chemical moiety having negatively charged functional group. In some embodiments, the anionic . In some embodiments, the anionic

cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, lithocholic acid, glycocholic acid, taurocholic acid, and tauroursodeoxycholic acid. Attorney Docket No. UAZ-43145.601 UA23-030 In some embodiments, the anionic component is selected from:

.

anionic carboxylate molecule selected from one of the following: , ,

, ,

, , , Attorney Docket No. UAZ-43145.601 UA23-030 In some embodiments, the anionic component is a negatively charged functional group selected from: butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, palmitic acid, undecylenic acid, oleic acid, linoleic acid, linolenic acid, myristoleic acid, ricinoleic acid, elaidic acid, N-decanoyl sarcosine, Lauryl sarcosine, docosahexaenoic acid, biotin, lactobionic acid, eicosapentaenoic acid, nervonic acid, Vitamin E succinate, 4-phenylbutyric acid, pamoic acid, α- lipoic acid, ibuprofen, naproxen, squalene acid, cholesterol hemisuccinate, capric acid, salcaprozic acid, docusic acid, cholic acid, glycocholic acid, taurocholic acid, tauroursodeoxycholic acid and other anionic bile acids, taurine, camphor sulfonic acid lauryl sulfate, cholesterol sulfate, DOPA, vitamin E phosphate, thiamine phosphate, saccharine sodium, acesulfame potassium, cyclamate sodium, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, gallic acid, vanillic acid, and phthalic acid. In some embodiments, the anionic component is an anionic carboxylate molecule selected from one of the following: , ,

, ,

, Attorney Docket No. UAZ-43145.601 UA23-030

In some embodiments, the anionic component is selected from a saturated fatty acid derivative moiety (carboxylate), an unsaturated fatty acid derivative moiety, an aromatic acid derivative moiety, a sulfonate derivative moiety, a sulfate derivative moiety, a phosphate derivative moiety, and a sulfamate derivative moiety. In some embodiments, the anionic component is selected from a negatively charged functional group of saturated fatty acids selected from butyric acid (butanoic acid), caproic acid (hexanoic acid), caprylic acid (octanoic acid), capric acid (decanoic acid)lauric acid (dodecanoic acid), palmitic acid (hexadecenoic acid), and cholic acid. In some embodiments, the anionic component is selected from a negatively charged functional group of unsaturated fatty acids selected from: undecylenic acid, oleic acid, linoleic acid, docosahexaenoic acid, eicosapentaenoic acid, nervonic acid, myristoleic acid, elaidic acid, and ricinoleic acid. In some embodiments, the anionic component is selected from a negatively charged functional group of aromatic acids selected from: salcaprozic acid, α-tocopherol succinate, 4- phenyl butyric acid, Ibuprofen, Naproxen, pamoic acid, Dolutegravir, Cabotegravir, and Bictegravir. In some embodiments, the anionic component is selected from a negatively charged functional group of sulfonate anions selected from: docusic acid, camphor sulfonic acid, taurocholic acid, tauroursodeoxycholic acid, and taurine. In some embodiments, the anionic component is selected from a negatively charged functional group of sulfate anions selected from: lauryl sulfate, and cholesterol sulfate. In some embodiments, the anionic component is selected from a negatively charged functional group of a phosphate anion selected from: α-tocopherol phosphate, 1,2-dioleoyl-sn- glycero-3-phosphate (DOPA), and thiamine phosphate. Attorney Docket No. UAZ-43145.601 UA23-030 In some embodiments, the anionic component is selected from a negatively charged functional group of sulfamate anions selected from: acesulfame, saccharin, and cyclamate. In some embodiments, the anionic component is selected from:

Attorney Docket No. UAZ-43145.601 UA23-030 In some embodiments, the anionic component is selected from a fatty anion, a docusate

Attorney Docket No. UAZ-43145.601 UA23-030 in a

ratio in the range of about 5:1 to about 1:5. In some embodiments, the ionic liquid formulation is a lipid nanoemulsion. In some embodiments, the ionic liquid formulation is associated with (e.g., encapsulated within) a nanoformulation. In some embodiments, the ionic liquid formulation is associated with (e.g., encapsulated within) a polymeric nanoformulation. In some embodiments, the ionic liquid formulation is associated with (e.g., encapsulated within) a nanomicelle (e.g., SoluPlus nanomicelle). In some embodiments, the ionic liquid formulation is associated with (e.g., encapsulated within) nanoformulations. In some embodiments, the ionic liquid formulation is associated with (e.g., encapsulated within) polymeric nanoformulations. In some embodiments, the ionic liquid formulation is associated with (e.g., encapsulated within) nanomicelles (e.g., SoluPlus nanomicelles). any one of the compositions and/or ionic liquid nanoformulations described herein, In certain embodiments, the present invention provides a pharmaceutical composition comprising an effective amount of a composition of or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In some embodiments, the composition further comprises at least one additional therapeutic agent. In some embodiments, the at least one additional therapeutic agent comprises any type or kind of therapeutic agent capable of inhibiting fungal activity. In some embodiments, the at least one additional therapeutic agent is selected from the following: a polyene, imidazole, triazole, thiazole, allylamine, echinocandin, among others. Examples include Amphotericin B, Attorney Docket No. UAZ-43145.601 UA23-030 Candicidin, Filipin, Hamycin, Natamycin, Nystatin, Rimocidin, Bifonazole, Butoconazole, Clotrimazole, econazole, fenticonazole, isoconazole, kentoconazole, miconazole, omoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, albaconazole, fluconazole, isavuconazole, itraconazole, posaconazole, ravuconazole, terconazole, voriconazole, abafungin, amorolfin, butenafine, naftifine, terbinafine, anidulafungin, caspofungin, micafungin, benzoic acid, ciclopirox, flucytosine, griseofulvin, haloprogin, polygodial, tolnaftate, undecylenic acid, and crystal violet. In certain embodiments, the present invention provides a method of treating or preventing a fungal infection in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of any one of the compositions and/or ionic liquid nanoformulations described herein. In some embodiments, the mammal is a human being. In some embodiments, the mammal is a human being suffering from or at risk of suffering from a fungal infection. In some embodiments, the fungal infection is an Aspergillus spp., Fusarium spp., Malassezia spp., Candida spp., or Cryptococcus spp. infection. In some embodiments, the fungal infection is an Aspergillus spp. infection. In some embodiments, the Aspergillus spp. infection is selected from an Aspergillus fumigatus infection, an Aspergillus favus infection, an Aspergillus niger infection, an Aspergillus terreus infection. In some embodiments, the fungal infection is a Fusarium spp. infection. In some embodiments, the Fusarium spp. infection is selected from a Fusarium solani infection, a Fusarium moniliforme infection, and a Fusarium proliferatum infection. In some embodiments, the fungal infection is an Malassezia spp. infection. In some embodiments, the Malassezia spp. infection is a Malassezia pachydermatis infection. In some embodiments, the fungal infection is a Candida spp. infection. In some embodiments, the Candida spp. infection is selected from a Candida albicans infection, a Candida glabrata infection, a Candida tropicalis infection, a Candida krusei infection, and a Candida auris infection. In some embodiments, the fungal infection is a Cryptococcus spp. infection. In some embodiments, the Cryptococcus spp. infection is a Cryptococcus neoformans infection. In some embodiments, the fungal infection is a Chrysosporium parvum, Metarhizium anisopliae, Phaeoisaria clematidis, or Sarcopodium oculorum infection. In some embodiments, the fungal infection is a Mucorales infection. In some embodiments, the Mucorales infection is a Mucor spp., Rhizopus spp., Lichtheimia spp., or Rhizomucor spp. Infection. In some embodiments, the Mucor spp. infection is a M. circinelloides infection; wherein the Rhizopus spp. infection is a Rhizopus delemar infection or Attorney Docket No. UAZ-43145.601 UA23-030 a Rhizopus oryzae infection; wherein the Lichtheimia spp. infection is a Lichtheimia corymbifera infection. In some embodiments, the method further comprises administering to the mammal in need thereof at least one additional therapeutic agent capable of inhibiting fungal activity. In some embodiments, the at least one additional therapeutic agent is selected from the following: a polyene, imidazole, triazole, thiazole, allylamine, echinocandin, among others. Examples include Amphotericin B, Candicidin, Filipin, Hamycin, Natamycin, Nystatin, Rimocidin, Bifonazole, Butoconazole, Clotrimazole, econazole, fenticonazole, isoconazole, kentoconazole, miconazole, omoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, albaconazole, fluconazole, isavuconazole, itraconazole, posaconazole, ravuconazole, terconazole, voriconazole, abafungin, amorolfin, butenafine, naftifine, terbinafine, anidulafungin, caspofungin, micafungin, benzoic acid, ciclopirox, flucytosine, griseofulvin, haloprogin, polygodial, tolnaftate, undecylenic acid, and crystal violet. In certain embodiments, the present invention provides a method of killing or inhibiting the growth of a fungus comprising contacting the fungus with a therapeutically effective amount of one or more of the compositions and/or ionic liquid nanoformulations described herein. In some embodiments, the fungus is selected from Aspergillus spp., Fusarium spp., Malassezia spp., Candida spp., or Cryptococcus spp.. In some embodiments, the fungus is selected from Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Fusarium solani, Fusarium moniliforme, Fusarium proliferatum, Malassezia pachydermatis, Candida albicans, Candida glabrata infection, Candida tropicalis, Candida krusei, Candida auris, Cryptococcus neoformans, Chrysosporium parvum, Metarhizium anisopliae, Phaeoisaria clematidis, Sarcopodium oculorum, M. circinelloides, Rhizopus delemar, Rhizopus oryzae, and Lichtheimia corymbifera. In certain embodiments, the present invention provides a use of one or more of the compositions or ionic liquid nanoformulations described herein, or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment or prevention of a fungal infection. In some embodiments, the fungal infection is related to one or more of: Aspergillus spp., Fusarium spp., Malassezia spp., Candida spp., and Cryptococcus spp.. In some embodiments, the fungal infection is related to one or more of: Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Fusarium solani, Fusarium moniliforme, Fusarium proliferatum, Malassezia pachydermatis, Candida albicans, Candida glabrata infection, Candida tropicalis, Candida krusei, Candida auris, Cryptococcus Attorney Docket No. UAZ-43145.601 UA23-030 neoformans, Chrysosporium parvum, Metarhizium anisopliae, Phaeoisaria clematidis, Sarcopodium oculorum, M. circinelloides, Rhizopus delemar, Rhizopus oryzae, and Lichtheimia corymbifera. In certain embodiments, the present invention provides a method of treating or preventing a parasitic infection in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of one or more of the compositions and/or ionic liquid nanoformulations described herein. In some embodiments, the mammal is a human being. In some embodiments, the mammal is a human being suffering from or at risk of suffering from a parasitic infection. In some embodiments, the parasitic infection is selected from African trypanosomiasis, amoebiasis, ascariasis, babesiosis, Chagas disease, cryptosporidiosis, cutaneous larva migrans, dirofilariasis, echinococcosis, fasciolosis, filariasis, lymphatic filariasis, giardiasis, helminthiasis, hookworm infection, leishmaniasis, visceral leishmaniasis, malaria, neurocysticercosis, onchocerciasis, protozoan infection, schistosomiasis, taeniasis, tapeworm infection, toxocariasis, toxoplasmosis, trichinosis, and zoonosis. In some embodiments, the method further comprises administering to the mammal an antiparasitic agent. In some embodiments, the antiparasitic agent is an antiprotozoal, an antihelminthic, an antinematode, an anticestode, an antitrematode, an antiamoebic, or an antifungal. In some embodiments, the antiparasitic agent is selected from albendazole, amphotericin B, benznidazole, bephenium, diethylcarbamzine, eflornithine, flubendazole, ivermectin, mebendazole, meglumine antimonite, melarsoprol, metronidazole, miltefosine, niclosamide, nifurtimox, nitazoxanide, pentavalent antimony, praziquantel, pyrantel, pyrvinium, sodium stibogluconate, thiabendazole, and tinidazole. In certain embodiments, the present invention provides a method of treating or preventing neurocysticercosis in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of one or more of the compositions and/or ionic liquid nanoformulations described herein. In some embodiments, the mammal is a human being. In some embodiments, the mammal is a human being suffering from or at risk of suffering from neurocysticercosis. In some embodiments, the method further comprises administering to the mammal an antiparasitic agent. In some embodiments, the antiparasitic agent is an antiprotozoal, an antihelminthic, an antinematode, an anticestode, an antitrematode, an antiamoebic, or an antifungal. In some embodiments, the antiparasitic agent is selected from albendazole, amphotericin B, benznidazole, bephenium, diethylcarbamzine, eflornithine, flubendazole, Attorney Docket No. UAZ-43145.601 UA23-030 ivermectin, mebendazole, meglumine antimonite, melarsoprol, metronidazole, miltefosine, niclosamide, nifurtimox, nitazoxanide, pentavalent antimony, praziquantel, pyrantel, pyrvinium, sodium stibogluconate, thiabendazole, and tinidazole. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1A-D: (A & B): Comparative oral pharmacokinetics (PK) studies on anthelmintic benzimidazoles (dosed at 20 mg/kg) in CD-1 mice (n=3) showed that only OXF plasma levels are ~4-fold greater than its IC₉₀ against C. neoformans indicating its suitability for oral CM therapy. (C) Mebendazole, fenbendazole or oxfendazole (OXF) were orally dosed (dose: 20 mg/kg once daily) to CD-1 mice (n≥4/group) infected with C. neoformans for 14 days and the fungal burden in lungs (CFU) was analyzed. Only OXF showed a significantly lower fungal burden in the lungs indicating its potential for oral CM therapy. (D) CD-1 mice (n≥4/group) infected with C. neoformans were treated daily with oral OXF suspension and survival was monitored compared to untreated control. OXF suspension treated mice showed 50% survival even after 50 days. FIG.2: Anthelmintic benzimidazoles including OXF show low and pH-dependent solubility (n≥3) which limits their oral delivery. FIG.3: Ionizable hydrophobic drugs with high crystallinity and low/no solubility in organic solvents and lipids can be converted into amphiphilic docusate-based ILs with no crystallinity, and high solubility in organic solvents and lipids using salt metathesis reaction.¹⁶ FIG.4A-E: Synthesis and characterization of oxfendazole docusate (OXF-Doc). (A) The scheme used to synthesize OXF-Doc. (B) OXF is a solid powder whereas OXF-Doc is a viscous IL. (C) 1H-NMR studies of OXF-Doc showed changes in the protons corresponding to pure OXF (labeled as “a”, “b”) and sodium docusate (labeled as “1”) indicating interaction. (D) The powder X-ray diffractometry and differential scanning calorimetry (E) showed the conversion of crystalline OXF to amorphous OXF-Doc. FIG.5A-B: Analysis of β-tubulin dynamics after treatment with ABZ, ABZ-Doc, or the sodium docusate (Doc) control. Cells expressing GFP-tagged β-tubulin were treated with ABZ, ABZ-Doc, or the control and imaged to assess β-tubulin dynamics and cell viability (Texas Red Live-or-Dye stain) at 1, 6, 24, 72, and 120 hours after treatment. A) Representative images from the 24 h timepoint show the formation of a multimera morphology and differences in viability after treatment ABZ or ABZ-Doc. B) ABZ and ABZ-Doc significantly reduced β-tubulin polymerization. Scale bar = 5 μm.¹⁶ Attorney Docket No. UAZ-43145.601 UA23-030 FIG.6A-B: The reference strain KN99α exhibits minimal tolerance and no resistance to OXF and OXF-Doc. KN99α was incubated with 5 µg/mL sodium docusate, OXF, or OXF-Doc as 12mL liquid cultures in RPMI. A) 300 µL aliquots were collected at various times and analyzed for resilience by culture on YPD for 48 hrs. Identification of viable colonies at 72 hours indicates the presence of resilient colonies. B) Plates were incubated an additional 48 hours to identify tolerant colonies. FIG.7: Structures of the OXF-ILs except OXF acesulfame and OXF saccharinate which are shown in Scheme 1. FIG.8A-D: (A) Transformation of pure solid OXF to IL, OXF-Doc, and subsequent incorporation of OXF-Doc into SoluPlus NM; (B) A representative TEM of OXF-Doc-SoluPlus NM (scale bar = 500 nm). (C) Evaluation of OXF-Doc: SoluPlus ratio ((n=3) on the micelle size and homogeneity (PDI). (D) OXF-Doc-SoluPlus NM maintained nanosize (< 80 nm) in buffers representative of gastrointestinal pH (n=3). FIG.9A-B: (A) Oral SoluPlus nanomicelles (NM) containing OXF docusate (OXF-Doc) showed significantly higher (~ 3.5-fold) OXF levels in plasma to oral OXF suspension in CD-1 mice (OXF dose: 20 mg/kg in all groups). Data expressed as mean ± S.D. (n ≥ 5/group; **P < 0.01). (B) Oral OXF-Doc-SoluPlus NM showed significantly higher lung and brain OXF levels compared to OXF suspension in CD-1 mice (OXF dose: 20 mg/kg in all groups). Data expressed as mean ± S.D. (n ≥ 3/group/time point; **P < 0.01). At 2 h, OXF-Doc-SoluPlus NM resulted in OXF brain levels (1110 ± 124 ng/g) > IC90 but < 2 X IC90 whereas OXF suspension showed sub- therapeutic OXF brain levels (294 ± 16 ng/g). FIG.10: Daily oral administration of OXF-Doc-SoluPlus NM (OXF: 20 mg/kg), OXF suspension (20 mg/kg), and vehicle control (SoluPlus) for 14 days was well tolerated by CD-1 mice (n≥ 4/group). FIG.11: Daily oral administration of OXF-Doc-SoluPlus NM (OXF: 20 mg/kg), OXF suspension (20 mg/kg), and vehicle control (SoluPlus) to CD-1 mice (n≥ 4/group) for 14 days did not show any abnormal changes in the liver function, kidney function, blood glucose level, and blood chemistry compared to untreated healthy CD-1 mice (P > 0.05). Oral OXF-Doc- SoluPlus NM were well tolerated by CD-1 mice despite significantly higher PK and biodistribution profile compared to OXF suspension. FIG.12: Unlike oral OXF suspension, oral OXF-Doc-SoluPlus NM showed dose- proportional in vivo antifungal effect in a mouse model of CM. Attorney Docket No. UAZ-43145.601 UA23-030 FIG.13A-BA: (A) KN99 infected CD-1 mice (n ≥ 7/group) treated daily with oral OXF- Doc SoluPlus NM (20 mg/kg OXF) showed 100% survival at day 75 whereas the OXF suspension group showed ~60% mortality at day 75 and untreated control group showed 100% mortality in 22 days. (B) The mice treated daily with oral OXF-Doc SoluPlus NM showed no detectable CFU in 30% of mice and low brain Cn burden in the rest of the mice. FIG.14: Schematic summarizing oral PK and biodistribution experiments to be carried out. FIG.15: Schematic summarizing oral PK and biodistribution experiments to identify three lead OXF-IL-SoluPlus NM formulations and to evaluate the dose-proportional PK of lead OXF-IL-SoluPlus NM formulations. FIG.16: Schematic summarizing in vivo safety studies to be carried out. FIG.17A-B: Murine models of cryptococcosis. A) The Early Treatment model is commonly used for antifungal drug testing where drug treatment is initiated one day prior to infection. B) The Late Treatment model initiates drug treatment after CNS dissemination at 10 days post infection. DETAILED DESCRIPTION OF THE INVENTION An ionic liquid (IL) is a low-melting salt containing organic/inorganic cation and anion, and depending upon the composition, IL can also be liquid at room temperature. Over the last 15 years, pharmaceutical applications of ILs have been on the rise. Conversion of ionizable active pharmaceutical ingredients (APIs) into ILs (API-ILs) using pharmaceutically acceptable counterions has emerged as a novel approach to modulate physicochemical and biopharmaceutical properties of ionizable drugs with poor solubility and/or permeability eventually leading to greater oral bioavailability. The anthelmintic benzimidazoles: albendazole (ABZ), mebendazole (MBZ), flubendazole (FBZ), triclabendazole (TCZ), fenbendazole (FNBZ), oxibendazole (OBZ), and oxfendazole (OXF) have broad-spectrum activity and are U.S. Food and Drug Administration (FDA)-approved for the treatment of various human and veterinary parasitic infections^7-11. Previously reported in vitro studies^12-16 and experiments conducted herein (see, Table 1) showed that MBZ, FBZ, TCZ, FNBZ, and OXF are active against C. neoformans at nM to µM concentrations in vitro, indicating their potential to be repurposed for CM therapy whereas OBZ and thiabendazole are inactive against C. neoformans¹³. However, there is a discrepancy between the in vitro and in vivo efficacy of anthelmintic benzimidazoles against C. neoformans, Attorney Docket No. UAZ-43145.601 UA23-030 with previous studies showing minimal in vivo activity when ABZ, FBZ, or FNBZ were given orally^14-15. Experiments conducted during the course of developing embodiments for the present invention pertained to oral pharmacokinetics (PK) studies on various anthelmintic benzimidazoles (20 mg/kg oral suspension). Such experiments indicated that only OXF attained plasma levels (Figure 1A) that were 4-fold greater than its IC90 against C. neoformans (Figure 1B) whereas other anthelmintic benzimidazoles showed limited plasma exposure (< IC₉₀ values). Our in vivo efficacy in CD-1 mice infected with C. neoformans showed that among various anthelmintic benzimidazoles, only OXF could significantly reduce the C. neoformans burden in the lungs (Figure 1C). Furthermore, it was shown that oral OXF suspension showed significant in vivo efficacy and improved survival in the murine CM model (Figure 1D). Moreover, such experiments demonstrate the ability of SoluPlus to package amphiphilic ILs to yield polymeric nanomicelles that can be delivered as an oral solution or can be freeze dried to obtain a solid powder. Such experiments further indicate that orally delivered SoluPlus nanomicelles containing oxfendazole docusate (OXF-Doc), an amphiphilic IL, resulted in significantly higher in vivo efficacy compared to pure OXF and OXF-Doc alone, which further underscores the benefits of our approach. Given that anthelmintic benzimidazoles are P-gp substrates with low oral bioavailability, the development of SoluPlus nanomicelles containing OXF ILs is an innovative approach to achieving improved oral bioavailability. Accordingly, the invention relates to a new class of oral bioavailability enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds. In particular, the present disclosure provides methods for treating or preventing infectious diseases with one or more oral bioavailability enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds, or pharmaceutically acceptable salts thereof, or compositions comprising the same and an additional anti-fungal agent, and pharmaceutical compositions comprising one or more oral bioavailability enhancing formulations of anthelmintic benzimidazole (e.g., oxfendazole) compounds and at least one additional anti-fungal agent. Section headings as used in this section and the entire disclosure herein are merely for organizational purposes and are not intended to be limiting. 1. Definitions Certain terms employed in the specification, examples, and appended claims are further described here in the present invention. These definitions should be read in light of the entire invention and as would be understood by a person skilled in art. Attorney Docket No. UAZ-43145.601 UA23-030 The terms “comprise(s),” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. The singular forms “a,” “and” and “the” include plural references unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments “comprising,” “consisting of,” and “consisting essentially of,” the embodiments or elements presented herein, whether explicitly set forth or not. For the recitation of numeric ranges herein, each intervening number there between with the same degree of precision is explicitly contemplated. For example, for the range of 6-9, the numbers 7 and 8 are contemplated in addition to 6 and 9, and for the range 6.0-7.0, the number 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are explicitly contemplated. Unless otherwise defined herein, scientific, and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear; in the event, however of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. As used herein, the terms “a” or “an” means “at least one” or “one or more” unless the context clearly indicates otherwise. As used herein, the term “about” means that the numerical value is approximate and small variations would not significantly affect the practice of the disclosed embodiments. Where a numerical limitation is used, unless indicated otherwise by the context, “about” means the numerical value can vary by +10% and remain within the scope of the disclosed embodiments. As used herein, “treat,” “treating,” and the like means a slowing, stopping, or reversing of progression of a disease or disorder when provided a composition (e.g., ionic liquid formulation) described herein to an appropriate control subject. The term also means a reversing of the progression of such a disease or disorder to a point of eliminating or greatly reducing the symptoms. As such, “treating” means an application or administration of the compositions described herein to a subject, where the subject has a disease or a symptom of a disease, where the purpose is to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disease or symptoms of the disease. Attorney Docket No. UAZ-43145.601 UA23-030 A “subject” or “patient” may be human or non-human and may include, for example, animal strains or species used as “model systems” for research purposes, such a mouse model as described herein. Likewise, patient may include either adults or juveniles (e.g., children). Moreover, patient may mean any living organism, preferably a mammal (e.g., humans and non- humans) that may benefit from the administration of compositions contemplated herein. Examples of mammals include, but are not limited to, any member of the Mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice and guinea pigs, and the like. Examples of non-mammals include, but are not limited to, birds, fish, and the like. In one embodiment, the mammal is a human. As used herein, the terms “providing,” “administering,” and “introducing,” are used interchangeably herein and refer to the placement of the compositions (e.g., ionic liquid formulations) of the disclosure into a subject by a method or route which results in at least partial localization of the compositions to a desired site. The compositions can be administered by any appropriate route which results in delivery to a desired location in the subject. Definitions of specific functional groups and chemical terms are described in more detail below. For purposes of this disclosure, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75^th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Sorrell, Organic Chemistry, 2^nd edition, University Science Books, Sausalito, 2006; Smith, March's Advanced Organic Chemistry: Reactions, Mechanism, and Structure, 7^th Edition, John Wiley & Sons, Inc., New York, 2013; Larock, Comprehensive Organic Transformations, 3^rd Edition, John Wiley & Sons, Inc., New York, 2018; and Carruthers, Some Modern Methods of Organic Synthesis, 3^rd Edition, Cambridge University Press, Cambridge, 1987; the entire contents of each of which are incorporated herein by reference. “Pharmacological composition” refers to a mixture of one or more of the compositions (e.g., ionic liquid formulations) described herein or pharmaceutically acceptable salts thereof, with other chemical components, such as pharmaceutically acceptable carriers and/or excipients. The purpose of a pharmacological composition is to facilitate administration of a composition to an organism. Attorney Docket No. UAZ-43145.601 UA23-030 “Pharmaceutically acceptable salts” is a cationic salt formed at any acidic (e.g., carboxylic acid) group, or an anionic salt formed at any basic (e.g., amino) group. “Solvate” is a physical association of a composition (e.g., ionic liquid formulation) of the invention with one or more solvent molecules, whether organic or inorganic. This physical association often includes hydrogen bonding. In certain instances, the solvate is capable of isolation, for example, when one or more solvate molecules are incorporated in the crystal lattice of the crystalline solid. “Solvate” encompasses both solution-phase and isolable solvates. Exemplary solvates include hydrates, ehanolates, and methanolates. “Prodrug” refers to a pharmacologically inactive derivative of a parent “drug” molecule which requires biotransformation within the target physiological system to release, or to convert the prodrug into the active drug. Prodrugs can address the problems associated with solubility, stability, cell permeability or bioavailability. Prodrugs usually comprise an active drug molecule and a chemical masking group. Prodrugs can be readily prepared from the parent compounds with well-known methods. The term “ionic liquids” as used herein refers to organic salts or mixtures of organic salts which exist in a liquid state. Ionic liquids have been shown to be useful in a variety of fields, including in industrial processing, catalysis, pharmaceuticals, and electrochemistry. The ionic liquids contain at least one anionic and at least one cationic component. Ionic liquids can comprise an additional hydrogen bond donor (i.e. any molecule that can provide an —OH or an —NH group); examples include but are not limited to alcohols, fatty acids, and amines. The anionic and the cationic component may be present in any molar ratio. 2. Ionic Liquid Formulations In certain aspects, the present disclosure provides an ionic liquid formulation comprising: a) a protonated compound encompassed within the following Formula I:

b) an anionic component, wherein “ ” is the anionic component; Attorney Docket No. UAZ-43145.601 UA23-030 wherein R1, R2, and the anionic component are chemical moieties that render the formulation a liquid at room temperature; wherein R1, R2, and the anionic component are chemical moieties that render the formulation with a melting point less than 100 degree C; wherein R1, R2, and the anionic component are chemical moieties that render the formulation as an amphiphilic liquid; wherein R1, R2, and the anionic component are chemical moieties that render the formulation a non-crystalline form; wherein R1, R2, and the anionic component are chemical moieties that render the formulation as therapeutically effective agent for treating a condition or disease known to be treatable with OXF; wherein R1, R2, and the anionic component are chemical moieties that render the formulation as having therapeutically effective antifungal activity; wherein R1, R2, and the anionic component are chemical moieties that render the formulation as having therapeutically effective antifungal activity against Cryptococcus neoformans; wherein R1, R2, and the anionic component are chemical moieties that render the formulation as therapeutically effective agent for perturbing microtubule assembly in Cryptococcus neoformans; wherein R1, R2, and the anionic component are chemical moieties that render the formulation as therapeutically effective agent for treating fungal disorders; wherein R1, R2, and the anionic component are chemical moieties that render the formulation as therapeutically effective agent for treating Cryptococcal meningitis (CM); wherein R1, R2, and the anionic component are chemical moieties that render the formulation as therapeutically effective agent for treating human neurocysticercosis wherein R1, R2, and the anionic component are chemical moieties that render the formulation as having enhanced bioavailability of the compound encompassed within Formula I; wherein R1, R2, and the anionic component are chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated within) with biodegradable polymers; wherein R1, R2, and the anionic component are chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated within) with biodegradable polymers thereby enhancing bioavailabity of the ionic liquid formulation; wherein R1, R2, and the anionic component are chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated within) with lipid nanoemulsions; and wherein R1, R2, and the anionic component are chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated within) with nanomicelles (e.g., SoluPlus nanomicelles) (e.g., lipid nanoemulsions). Attorney Docket No. UAZ-43145.601 UA23-030 In some embodiments, R1 is not limited to a particular chemical moiety. In some O (substituted or unsubstituted). In to a particular chemical moiety. In some

or (C1-C6) alkyl. In some embodiments, R2 is methyl. In some embodiments, the anionic component ( ) is not limited to a particular chemical moiety. In some embodiments, the anionic component is selected from an anionic therapeutic agent, an anionic amino acid, an anionic nutraceutical, an anionic agrochemical molecule, an anionic functional food, an anionic excipient, and a pharmaceutically acceptable anion. In some embodiments, the anionic component is an anionic carboxylate, an anionic sulfonate, an anionic sulfate, an anionic phosphate, an anionic phosphonate, an anionic sulfamate, or a chemical moiety having negatively charged functional group. In some embodiments, the anionic . In some embodiments, the anionic

acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, lithocholic acid, glycocholic acid, taurocholic acid, and tauroursodeoxycholic acid.

Attorney Docket No. UAZ-43145.601 UA23-030 In some embodiments, the anionic component is selected from: .

is an anionic carboxylate molecule selected from one of the following: , ,

, ,

, .

anionic component is a negatively charged functional group selected from: butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, palmitic acid, undecylenic acid, oleic acid, linoleic acid, linolenic acid, myristoleic acid, ricinoleic acid, elaidic Attorney Docket No. UAZ-43145.601 UA23-030 acid, N-decanoyl sarcosine, Lauryl sarcosine, docosahexaenoic acid, biotin, lactobionic acid, eicosapentaenoic acid, nervonic acid, Vitamin E succinate, 4-phenylbutyric acid, pamoic acid, α- lipoic acid, ibuprofen, naproxen, squalene acid, cholesterol hemisuccinate, capric acid, salcaprozic acid, docusic acid, cholic acid, glycocholic acid, taurocholic acid, tauroursodeoxycholic acid and other anionic bile acids, taurine, camphor sulfonic acid lauryl sulfate, cholesterol sulfate, DOPA, vitamin E phosphate, thiamine phosphate, saccharine sodium, acesulfame potassium, cyclamate sodium, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, gallic acid, vanillic acid, and phthalic acid. In some embodiments, the anionic component is an anionic carboxylate molecule selected from one of the following: , ,

,

Attorney Docket No. UAZ-43145.601 UA23-030

In some embodiments, the anionic component is selected from a saturated fatty acid derivative moiety (carboxylate), an unsaturated fatty acid derivative moiety, an aromatic acid derivative moiety, a sulfonate derivative moiety, a sulfate derivative moiety, a phosphate derivative moiety, and a sulfamate derivative moiety. In some embodiments, the anionic component is selected from a negatively charged functional group of saturated fatty acids selected from butyric acid (butanoic acid), caproic acid (hexanoic acid), caprylic acid (octanoic acid), capric acid (decanoic acid)lauric acid (dodecanoic acid), palmitic acid (hexadecenoic acid), and cholic acid. In some embodiments, the anionic component is selected from a negatively charged functional group of unsaturated fatty acids selected from: undecylenic acid, oleic acid, linoleic acid, docosahexaenoic acid, eicosapentaenoic acid, nervonic acid, myristoleic acid, elaidic acid, and ricinoleic acid. In some embodiments, the anionic component is selected from a negatively charged functional group of aromatic acids selected from: salcaprozic acid, α-tocopherol succinate, 4- phenyl butyric acid, Ibuprofen, Naproxen, pamoic acid, Dolutegravir, Cabotegravir, and Bictegravir. In some embodiments, the anionic component is selected from a negatively charged functional group of sulfonate anions selected from: docusic acid, camphor sulfonic acid, taurocholic acid, tauroursodeoxycholic acid, and taurine. In some embodiments, the anionic component is selected from a negatively charged functional group of sulfate anions selected from: lauryl sulfate, and cholesterol sulfate. In some embodiments, the anionic component is selected from a negatively charged functional group of a phosphate anion selected from: α-tocopherol phosphate, 1,2-dioleoyl-sn- glycero-3-phosphate (DOPA), and thiamine phosphate. Attorney Docket No. UAZ-43145.601 UA23-030 In some embodiments, the anionic component is selected from a negatively charged functional group of sulfamate anions selected from: acesulfame, saccharin, and cyclamate. In some embodiments, the anionic component is selected from: .

Attorney Docket No. UAZ-43145.601 UA23-030 In some embodiments, the anionic component is selected from a fatty anion, a docusate

Attorney Docket No. UAZ-43145.601 UA23-030 wherein

asymmetric or chiral centers are present. The stereoisomer is “R” or “S” depending on the configuration of substituents around the chiral carbon atom. The terms “R” and “S” used herein are configurations as defined in IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, in Pure Appl. Chem., 1976, 45: 13-30. The disclosure contemplates various stereoisomers and mixtures thereof and these are specifically included within the scope of this disclosure. Stereoisomers include enantiomers and diastereomers, and mixtures of enantiomers or diastereomers. Individual stereoisomers of the compounds may be prepared synthetically from commercially available starting materials, which contain asymmetric or chiral centers or by preparation of racemic mixtures followed by methods of resolution well-known to those of ordinary skill in the art. These methods of resolution are exemplified by (1) attachment of a mixture of enantiomers to a chiral auxiliary, separation of the resulting mixture of diastereomers by recrystallization or chromatography and optional liberation of the optically pure product from the auxiliary as described in Furniss, Hannaford, Smith, and Tatchell, “Vogel's Textbook of Practical Organic Chemistry,” 5th edition (1989), Longman Scientific & Technical, Essex CM20 2JE, England (or more recent versions thereof), or (2) direct separation of the mixture of optical enantiomers on chiral chromatographic columns, or (3) fractional recrystallization methods. It should be understood that the compounds may possess tautomeric forms, as well as geometric isomers, and that these also constitute embodiments of the disclosure. In some embodiments, the ionic liquid formulations can be combined with another solvent to enhance solubility and/or delivery. The solvent may be aqueous or non-aqueous. In Attorney Docket No. UAZ-43145.601 UA23-030 some embodiments, the purpose of the solvent is to control the dose of the ionic liquid. Dilution of the ionic liquid by the solvent can serve the purpose of delivering a safe dose to the subject. In some embodiments, the purpose of the solvent is to improve solubility of the one or more drugs. Such improvements may come from the ability of the solvent to control the physicochemical environment of the ionic liquid to match the chemical properties of the one or more drugs. The solvents used may include without limitation: sterile water, saline solution, glycerin, propylene glycol, ethanol, oils, ethyl oleate, isopropyl myristate, benzyl benzoate, or surfactants. In some embodiments, the solvent is chosen so as to not adversely impact the compatibility of the ionic liquid formulation. In some embodiments, a composition as described herein, e.g., a composition comprising ionic liquid formulations and one or more drugs, can further comprise a pharmaceutically acceptable excipient. Suitable excipients include, for example, water, saline, glycerol, ethanol, or the like, and combinations thereof. In addition, if desired, the composition can contain minor amounts of additional excipients such as emulsifying agents, surfactants, pH buffering agents, and the like, which enhance the effectiveness of the ionic liquid formulation. In some embodiments, the ionic liquid formulation may be further encapsulated in a dosage form designed to facilitate delivery to an organism. Non-limiting examples of such dosage forms include capsules, tablets, and syrups. In some embodiments, the ionic liquid formulation may require excipients sugars (such as lactose), starches (such as corn starch), cellulose, cellulose derivatives (such as sodium carboxymethyl cellulose), gelatin, and other compatible substances. In some embodiments, the ionic liquid formulation described herein further comprises one or more additional agents. In some embodiments, the one or more additional agents are selected from a nucleic acid, a small molecule, and a polypeptide. In some embodiments, the one or more additional agents comprise a nucleic acid. In some embodiments, the one or more additional agents comprise a small molecule. In some embodiments, the one or more additional agents comprise a polypeptide. In some embodiments the polypeptide comprises an antibody. In some embodiments, the antibody comprises any one selected from Fragment Antigen-binding (Fab, F(ab′)₂), single chain variable fragment (scFv), and nanobodies. Attorney Docket No. UAZ-43145.601 UA23-030 The present disclosure also includes isotopically-labeled compounds, which is identical to those recited in Formula I but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes include those for hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, such as, but not limited to ²H, ³H, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O, ³¹P, ³²P , ³⁵S, ¹⁸F, and ³⁶Cl, respectively. Substitution with heavier isotopes such as deuterium, for example, ²H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances. The compound may incorporate positron- emitting isotopes for medical imaging and positron-emitting tomography (PET) studies. Suitable positron-emitting isotopes that can be incorporated in compounds of formula (I) are ¹¹C, ¹³N, ¹⁵O, and ¹⁸F. Isotopically-labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the accompanying Examples using appropriate isotopically-labeled reagent in place of non-isotopically-labeled reagent. In certain embodiments, the ionic liquid formulations described herein are associated (e.g., encapsulated) with biodegradable polymers (e.g., for purposes of enhancing bioavailability). In some embodiments, the biodegradable polymer is a lipid nanoemulsion. In some embodiments, the biodegradable polymer is nanomicelle. In some embodiments, the biodegradable polymer is SoluPlus nanomicelles. Such ionic liquid formulations as described herein may be synthesized according to a variety of methods. Reaction conditions and reaction times for each individual step can vary depending on the particular reactants employed and substituents present in the reactants used. Reactions can be worked up in the conventional manner, e.g., by eliminating the solvent from the residue and further purified according to methodologies generally known in the art such as, but not limited to, crystallization, distillation, extraction, trituration, and chromatography. Unless otherwise described, the starting materials and reagents are either commercially available or can be prepared by one skilled in the art from commercially available materials using methods described in the chemical literature. Starting materials, if not commercially available, can be prepared by procedures selected from standard organic chemical techniques, techniques that are analogous to the synthesis of known, structurally similar compounds, or techniques that are analogous to the above described scheme. Attorney Docket No. UAZ-43145.601 UA23-030 Routine experimentations, including appropriate manipulation of the reaction conditions, reagents and sequence of the synthetic route, protection of any chemical functionality that cannot be compatible with the reaction conditions, and deprotection at a suitable point in the reaction sequence of the method are included in the scope of the disclosure. Suitable protecting groups and the methods for protecting and deprotecting different substituents using such suitable protecting groups are well known to those skilled in the art; examples of which can be found in PGM Wuts and TW Greene, in Greene's book titled Protective Groups in Organic Synthesis (4th ed.), John Wiley & Sons, NY (2006), which is incorporated herein by reference in its entirety. Synthesis of the ionic liquid formulations of the disclosure can be accomplished by methods analogous to those described in the synthetic schemes described hereinabove and in specific examples. When an optically active form of a disclosed compound within the ionic liquid formulations is required, it can be obtained by carrying out one of the procedures described herein using an optically active starting material (prepared, for example, by asymmetric induction of a suitable reaction step), or by resolution of a mixture of the stereoisomers of the compound or intermediates using a standard procedure (such as chromatographic separation, recrystallization, or enzymatic resolution). Similarly, when a pure geometric isomer of a compound within the ionic liquid formulations is required, it can be obtained by carrying out one of the above procedures using a pure geometric isomer as a starting material, or by resolution of a mixture of the geometric isomers of the compound or intermediates using a standard procedure such as chromatographic separation. 3. Compositions The disclosed ionic liquid formulations may be incorporated into compositions that may be suitable for administration to a subject (such as a patient, which may be a human or non- human). 3a. Pharmaceutical Compositions The disclosed ionic liquid formulations may be incorporated into pharmaceutically acceptable compositions. The pharmaceutical compositions may include a “therapeutically effective amount” or a “prophylactically effective amount” of the ionic liquid formulations. A “therapeutically effective amount” refers to an amount effective, at dosages and for periods of Attorney Docket No. UAZ-43145.601 UA23-030 time necessary, to achieve the desired therapeutic result. A therapeutically effective amount of the composition may be determined by a person skilled in the art and may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the composition to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or detrimental effects of the ionic liquid formulations are outweighed by the therapeutically beneficial effects. A “prophylactically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically effective amount. The pharmaceutical compositions and formulations may include pharmaceutically acceptable carriers. The term “pharmaceutically acceptable carrier,” as used herein, means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material, surfactant, cyclodextrins or formulation auxiliary of any type. Some examples of materials which can serve as pharmaceutically acceptable carriers are sugars such as, but not limited to, lactose, glucose and sucrose; starches such as, but not limited to, corn starch and potato starch; cellulose and its derivatives such as, but not limited to, sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as, but not limited to, cocoa butter and suppository waxes; oils such as, but not limited to, peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; surfactants such as, but not limited to, cremophor EL, cremophor RH 60, Solutol HS 15 and polysorbate 80; cyclodextrins such as, but not limited to, alpha-CD, beta-CD, gamma-CD, HP-beta-CD, SBE-beta-CD; glycols; such as propylene glycol; esters such as, but not limited to, ethyl oleate and ethyl laurate; agar; buffering agents such as, but not limited to, magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as, but not limited to, sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. The route by which the disclosed ionic liquid formulations are administered and the form of the composition will dictate the type of carrier to be used. The composition may be in a variety of forms, suitable, for example, for systemic administration (e.g., oral, rectal, nasal, sublingual, buccal, implants, or parenteral injections) or topical administration (e.g., dermal, Attorney Docket No. UAZ-43145.601 UA23-030 pulmonary, nasal, aural, ocular, liposome delivery systems, or iontophoresis). In some embodiments, the composition is for oral administration. In some embodiments, the composition is for subcutaneous administration. In some embodiments, the composition is for intravenous administration. Carriers for systemic administration typically include at least one of diluents, lubricants, binders, disintegrants, colorants, flavors, sweeteners, antioxidants, preservatives, glidants, solvents, suspending agents, wetting agents, surfactants, cyclodextrins combinations thereof, and others. All carriers are optional in the compositions. Suitable diluents include sugars such as glucose, lactose, dextrose, and sucrose; diols such as propylene glycol; calcium carbonate; sodium carbonate; sugar alcohols, such as glycerin; mannitol; and sorbitol. The amount of diluent(s) in a systemic or topical composition is typically about 50 to about 90%. Suitable lubricants include silica, talc, stearic acid and its magnesium salts and calcium salts, calcium sulfate; and liquid lubricants such as polyethylene glycol and vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil and oil of theobroma. The amount of lubricant(s) in a systemic or topical composition is typically about 5 to about 10%. Suitable binders include polyvinyl pyrrolidone; magnesium aluminum silicate; starches such as corn starch and potato starch; gelatin; tragacanth; and cellulose and its derivatives, such as sodium carboxymethylcellulose, ethyl cellulose, methylcellulose, microcrystalline cellulose, and sodium carboxymethylcellulose. The amount of binder(s) in a systemic composition is typically about 5 to about 50%. Suitable disintegrants include agar, alginic acid and the sodium salt thereof, effervescent mixtures, croscarmellose, crospovidone, sodium carboxymethyl starch, sodium starch glycolate, clays, and ion exchange resins. The amount of disintegrant(s) in a systemic or topical composition is typically about 0.1 to about 10%. Suitable colorants include a colorant such as an FD&C dye. When used, the amount of colorant in a systemic or topical composition is typically about 0.005 to about 0.1%. Suitable flavors include menthol, peppermint, and fruit flavors. The amount of flavor(s), when used, in a systemic or topical composition is typically about 0.1 to about 1.0%. Suitable sweeteners include aspartame and saccharin. The amount of sweetener(s) in a systemic or topical composition is typically about 0.001 to about 1%. Attorney Docket No. UAZ-43145.601 UA23-030 Suitable antioxidants include butylated hydroxyanisole (“BHA”), butylated hydroxytoluene (“BHT”), and vitamin E. The amount of antioxidant(s) in a systemic or topical composition is typically about 0.1 to about 5%. Suitable preservatives include benzalkonium chloride, methyl paraben and sodium benzoate. The amount of preservative(s) in a systemic or topical composition is typically about 0.01 to about 5%. Suitable glidants include silicon dioxide. The amount of glidant(s) in a systemic or topical composition is typically about 1 to about 5%. Suitable solvents include water, isotonic saline, ethyl oleate, glycerine, hydroxylated castor oils, alcohols such as ethanol, dimethyl sulfoxide, N-methyl-2-pyrrolidone, dimethylacetamide and phosphate (or other suitable buffer). The amount of solvent(s) in a systemic or topical composition is typically from about 0 to about 100%. Suitable suspending agents include AVICEL RC-591 (from FMC Corporation of Philadelphia, Pa.) and sodium alginate. The amount of suspending agent(s) in a systemic or topical composition is typically about 1 to about 8%. Suitable surfactants include lecithin, Polysorbate 80, and sodium lauryl sulfate, and the TWEENS from Atlas Powder Company of Wilmington, Del. Suitable surfactants include those disclosed in the C.T.F.A. Cosmetic Ingredient Handbook, 1992, pp.587-592; Remington's Pharmaceutical Sciences, 15th Ed.1975, pp.335-337; and McCutcheon's Volume 1, Emulsifiers & Detergents, 1994, North American Edition, pp.236-239. The amount of surfactant(s) in the systemic or topical composition is typically about 0.1% to about 5%. Suitable cyclodextrins include alpha-CD, beta-CD, gamma-CD, hydroxypropyl betadex (HP-beta-CD), sulfobutyl-ether β-cyclodextrin (SBE-beta-CD). The amount of cyclodextrins in the systemic or topical composition is typically about 0% to about 40%. Although the amounts of components in the systemic compositions may vary depending on the type of systemic composition prepared, in general, systemic compositions include 0.01% to 50% of an active compound (e.g., an ionic liquid formulation as described herein) and 50% to 99.99% of one or more carriers. Compositions for parenteral administration typically include 0.1% to 10% of actives and 90% to 99.9% of a carrier including a diluent and a solvent. Compositions for oral administration can have various dosage forms. For example, solid forms include tablets, capsules, granules, and bulk powders. These oral dosage forms include a safe and effective amount, usually at least about 5%, and more particularly from about 25% to Attorney Docket No. UAZ-43145.601 UA23-030 about 50% of actives. The oral dosage compositions include about 50% to about 95% of carriers, and more particularly, from about 50% to about 75%. Tablets can be compressed, tablet triturates, enteric-coated, sugar-coated, film-coated, or multiple-compressed. Tablets typically include an active component, and a carrier comprising ingredients selected from diluents, lubricants, binders, disintegrants, colorants, flavors, sweeteners, glidants, and combinations thereof. Specific diluents include calcium carbonate, sodium carbonate, mannitol, lactose, and cellulose. Specific binders include starch, gelatin, and sucrose. Specific disintegrants include alginic acid and croscarmellose. Specific lubricants include magnesium stearate, stearic acid, and talc. Specific colorants are the FD&C dyes, which can be added for appearance. Chewable tablets preferably contain sweeteners such as aspartame and saccharin, or flavors such as menthol, peppermint, fruit flavors, or a combination thereof. Capsules (including implants, time release and sustained release formulations) typically include an active ionic liquid formulation, and a carrier including one or more diluents disclosed above in a capsule comprising gelatin. Granules typically comprise a disclosed ionic liquid formulation, and preferably glidants such as silicon dioxide to improve flow characteristics. Implants can be of the biodegradable or the non-biodegradable type. The selection of ingredients in the carrier for oral compositions depends on secondary considerations like taste, cost, and shelf stability, which are not critical for the purposes of this invention. Solid compositions may be coated by conventional methods, typically with pH or time- dependent coatings, such that a disclosed ionic liquid formulation is released in the gastrointestinal tract in the vicinity of the desired application, or at various points and times to extend the desired action. The coatings typically include one or more components selected from the group consisting of cellulose acetate phthalate, polyvinyl acetate phthalate, hydroxypropyl methyl cellulose phthalate, ethyl cellulose, EUDRAGIT® coatings (available from Evonik Industries of Essen, Germany), waxes and shellac. Compositions for oral administration can have liquid forms. For example, suitable liquid forms include aqueous solutions, emulsions, suspensions, solutions reconstituted from non- effervescent granules, suspensions reconstituted from non-effervescent granules, effervescent preparations reconstituted from effervescent granules, elixirs, tinctures, syrups, and the like. Liquid orally administered compositions typically include a disclosed ionic liquid formulation and a carrier, namely, a carrier selected from diluents, colorants, flavors, sweeteners, Attorney Docket No. UAZ-43145.601 UA23-030 preservatives, solvents, suspending agents, and surfactants. Peroral liquid compositions preferably include one or more ingredients selected from colorants, flavors, and sweeteners. Other compositions useful for attaining systemic delivery of the ionic liquid formulations to the subject include sublingual, buccal and nasal dosage forms. Such compositions typically include one or more of soluble filler substances such as diluents including sucrose, sorbitol, and mannitol; and binders such as acacia, microcrystalline cellulose, carboxymethyl cellulose, and hydroxypropyl methylcellulose. Such compositions may further include lubricants, colorants, flavors, sweeteners, antioxidants, and glidants. The disclosed ionic liquid formulations can be topically administered. Topical compositions that can be applied locally to the skin may be in any form including solids, solutions, oils, creams, ointments, gels, lotions, shampoos, leave-on and rinse-out hair conditioners, milks, cleansers, moisturizers, sprays, skin patches, and the like. Topical compositions include: a disclosed ionic liquid formulation, and a carrier. The carrier of the topical composition preferably aids penetration of the ionic liquid formulation into the skin. The carrier may further include one or more optional components. The amount of the carrier employed in conjunction with a disclosed ionic liquid formulation is sufficient to provide a practical quantity of composition for administration per unit dose of the ionic liquid formulation. Techniques and compositions for making dosage forms useful in the methods of this invention are described in the following references: Modern Pharmaceutics, Chapters 9 and 10, Banker & Rhodes, eds. (1979); Lieberman et al., Pharmaceutical Dosage Forms: Tablets (1981); and Ansel, Introduction to Pharmaceutical Dosage Forms, 2nd Ed., (1976). A carrier may include a single ingredient or a combination of two or more ingredients. In the topical compositions, the carrier includes a topical carrier. Suitable topical carriers include one or more ingredients selected from phosphate buffered saline, isotonic water, deionized water, monofunctional alcohols, symmetrical alcohols, aloe vera gel, allantoin, glycerin, vitamin A and E oils, mineral oil, propylene glycol, PPG-2 myristyl propionate, dimethyl isosorbide, castor oil, combinations thereof, and the like. More particularly, carriers for skin applications include propylene glycol, dimethyl isosorbide, and water, and even more particularly, phosphate buffered saline, isotonic water, deionized water, monofunctional alcohols, and symmetrical alcohols. Attorney Docket No. UAZ-43145.601 UA23-030 The carrier of a topical composition may further include one or more ingredients selected from emollients, propellants, solvents, humectants, thickeners, powders, fragrances, pigments, and preservatives, all of which are optional. Suitable emollients include stearyl alcohol, glyceryl monoricinoleate, glyceryl monostearate, propane-1,2-diol, butane-1,3-diol, mink oil, cetyl alcohol, isopropyl isostearate, stearic acid, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, cetyl palmitate, di-n-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, sesame oil, coconut oil, arachis oil, castor oil, acetylated lanolin alcohols, petroleum, mineral oil, butyl myristate, isostearic acid, palmitic acid, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate, and combinations thereof. Specific emollients for skin include stearyl alcohol and polydimethylsiloxane. The amount of emollient(s) in a skin-based topical composition is typically about 5% to about 95%. Suitable propellants include propane, butane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide, and combinations thereof. The amount of propellant(s) in a topical composition is typically about 0% to about 95%. Suitable solvents include water, ethyl alcohol, methylene chloride, isopropanol, castor oil, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethylsulfoxide, dimethyl formamide, tetrahydrofuran, and combinations thereof. Specific solvents include ethyl alcohol and homotopic alcohols. The amount of solvent(s) in a topical composition is typically about 0% to about 95%. Suitable humectants include glycerin, sorbitol, sodium 2-pyrrolidone-5-carboxylate, soluble collagen, dibutyl phthalate, gelatin, and combinations thereof. Specific humectants include glycerin. The amount of humectant(s) in a topical composition is typically 0% to 95%. The amount of thickener(s) in a topical composition is typically about 0% to about 95%. Suitable powders include beta-cyclodextrins, hydroxypropyl cyclodextrins, chalk, talc, fullers earth, kaolin, starch, gums, colloidal silicon dioxide, sodium polyacrylate, tetra alkyl ammonium smectites, trialkyl aryl ammonium smectites, chemically-modified magnesium aluminum silicate, organically-modified montmorillonite clay, hydrated aluminum silicate, fumed silica, carboxyvinyl polymer, sodium carboxymethyl cellulose, ethylene glycol monostearate, and combinations thereof. The amount of powder(s) in a topical composition is typically 0% to 95%. Attorney Docket No. UAZ-43145.601 UA23-030 The amount of fragrance in a topical composition is typically about 0% to about 0.5%, particularly, about 0.001% to about 0.1%. Suitable pH adjusting additives include HCl or NaOH in amounts sufficient to adjust the pH of a topical pharmaceutical composition. 3a. Additional Therapeutic Agents Any of the above compositions or formulations disclosed herein may further comprise at least one additional therapeutic agent. In some embodiments the at least one additional therapeutic agent is one or more other anti-fungal agents. In some embodiments, the composition comprises any one or more of the ionic liquid formulations, or a pharmaceutically acceptable salt thereof, and one or more other anti-fungal agent(s). In some embodiments, the other anti-fungal agent is an azole or an echinocandin. In some embodiments, the other anti-fungal agent is an azole. In some embodiments, the azole is itraconazole, posaconazole, voriconazole (VOR), or isavuconazole. In some embodiments, the azole is itraconazole. In some embodiments, the azole is posaconazole. In some embodiments, the azole is voriconazole. In some embodiments, the azole is isavuconazole. In some embodiments, the other anti-fungal agent is an echinocandin. In some embodiments, the echinocandin is caspofungin (CAS). In some embodiments, the other anti-fungal agent is nystatin, miconazole, Gentian violet, or amphotericin B. In some embodiments, the other anti- fungal agent is nystatin. In some embodiments, the other anti-fungal agent is miconazole. In some embodiments, the other anti-fungal agent is Gentian violet. In some embodiments, the other anti-fungal agent is amphotericin B. Additional anti-fungal agents include, but are not limited to, fosmanogepix, ibrexafungerp, olorofim, opelconazole, and rezafungin. In some embodiments, the other anti-fungal agent is fosmanogepix. In some embodiments, the other anti- fungal agent is ibrexafungerp. In some embodiments, the other anti-fungal agent is olorofim. In some embodiments, the other anti-fungal agent is opelconazole. In some embodiments, the other anti-fungal agent is rezafungin. In some embodiments, the other anti-fungal agent is Nikkomycin Z. Other anti-fungal agents include VT-1129, VT-1161, VT-1598, PC1244, SUBA- ITC, CAMB, MGCD290, T-2307, and VL-2397. Additional anti-fungal agents are disclosed in, for example, PCT Publication No. WO 2021/247781. In embodiments, the antifungal agent is a known antifungal and not an ionic liquid formulation described herein, such as a polyene, imidazole, triazole, thiazole, allylamine, echinocandin, among others. Examples include Amphotericin B, Candicidin, Filipin, Hamycin, Attorney Docket No. UAZ-43145.601 UA23-030 Natamycin, Nystatin, Rimocidin, Bifonazole, Butoconazole, Clotrimazole, econazole, fenticonazole, isoconazole, kentoconazole, miconazole, omoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, albaconazole, fluconazole, isavuconazole, itraconazole, posaconazole, ravuconazole, terconazole, voriconazole, abafungin, amorolfin, butenafine, naftifine, terbinafine, anidulafungin, caspofungin, micafungin, benzoic acid, ciclopirox, flucytosine, griseofulvin, haloprogin, polygodial, tolnaftate, undecylenic acid, and crystal violet, among others. In some embodiments, the at least one additional therapeutic agent comprises a polynucleotide or nucleic acid (e.g., ribonucleic acid or deoxyribonucleic acid). The term “polynucleotide,” in its broadest sense, includes any compound and/or substance that is or can be incorporated into an oligonucleotide chain. Exemplary polynucleotides for use in accordance with the present disclosure include, but are not limited to, one or more of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) including messenger mRNA (mRNA), hybrids thereof, RNAi- inducing agents, RNAi agents, siRNAs, shRNAs, miRNAs, antisense RNAs, ribozymes, catalytic DNA, RNAs that induce triple helix formation, aptamers, vectors, etc. In some embodiments, the at least one additional therapeutic agent is an RNA. RNAs useful in the compositions and methods described herein can be selected from the group consisting of, but are not limited to, shortmers, antagomirs, antisense RNAs, ribozymes, small interfering RNA (siRNA), asymmetrical interfering RNA (aiRNA), microRNA (miRNA), Dicer-substrate RNA (dsRNA), small hairpin RNA (shRNA), transfer RNA (tRNA), messenger RNA (mRNA), and mixtures thereof. In certain embodiments, the at least one additional therapeutic agent is an mRNA. An mRNA may encode any polypeptide of interest, including any naturally or non-naturally occurring or otherwise modified polypeptide. A polypeptide encoded by an mRNA may be of any size and may have any secondary structure or activity. In some embodiments, a polypeptide encoded by an mRNA may have a therapeutic effect when expressed in a cell. In other embodiments, the at least one additional therapeutic agent is an siRNA. An siRNA may be capable of selectively knocking down or down regulating expression of a gene of interest. For example, an siRNA could be selected to silence a gene associated with a particular disease, disorder, or condition upon administration to a subject in need thereof of a nanoparticle composition including the siRNA. An siRNA may comprise a sequence that is complementary to an mRNA sequence that encodes a gene or protein of interest. In some embodiments, the siRNA may be an immunomodulatory siRNA. Attorney Docket No. UAZ-43145.601 UA23-030 In some embodiments, the at least one additional therapeutic agent is an shRNA or a vector or plasmid encoding the same. An shRNA may be produced inside a target cell upon delivery of an appropriate construct to the nucleus. Constructs and mechanisms relating to shRNA are well known in the relevant arts. 4. Methods of Use The disclosure further provides methods for treating a disease or disorder comprising administration of ionic liquid formulation as disclosed herein, to a subject in need thereof. In some embodiments, the subject is a human. The present disclosure provides methods of treating or preventing a Cryptococcus fungal infection in a mammal comprising administering to the mammal in need thereof an ionic liquid formulation. The present disclosure also provides methods of killing or inhibiting the growth of a Cryptococcus species comprising contacting the Cryptococcus species with ionic liquid formulations. The present disclosure provides methods of treating or preventing a fungal infection in a mammal comprising administering to the mammal in need thereof ionic liquid formulations in combination with one or more other anti-fungal agent(s) (i.e., in the same ionic liquid formulation or in separate pharmaceutical compositions). The present disclosure also provides methods of killing or inhibiting the growth of a fungus comprising contacting the fungus with ionic liquid formulations in combination with one or more other anti-fungal agent(s) (i.e., in the same ionic liquid formulation or in separate pharmaceutical compositions). In some embodiments, the fungus is, or the fungal infection is caused by, Aspergillus spp. (e.g., Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus), Fusarium spp. (e.g., Fusarium solani, Fusarium moniliforme, and Fusarium proliferatum), Malassezia spp. (e.g., Malassezia pachydermatis), Candida spp. (e.g., Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, and Candida auris), or Cryptococcus spp. (e.g., Cryptococcus neoformans), Mucorales such as Mucor spp. (e.g., M. circinelloides), Rhizopus spp. (e.g., Rhizopus delemar and Rhizopus oryzae), Lichtheimia spp. (e.g., Lichtheimia corymbifera), and Rhizomucor spp., or Chrysosporium parvum, Metarhizium anisopliae, Phaeoisaria clematidis, or Sarcopodium oculorum. In some embodiments, the fungus is, or the fungal infection is caused Attorney Docket No. UAZ-43145.601 UA23-030 by, Aspergillus spp., Fusarium spp., Malassezia spp., Candida spp., or Cryptococcus spp. In some embodiments, the fungus is, or the fungal infection is caused by, Aspergillus spp. In some embodiments, the fungus is, or the fungal infection is caused by, Aspergillus fumigatus. In some embodiments, the fungus is, or the fungal infection is caused by, Aspergillus flavus. In some embodiments, the fungus is, or the fungal infection is caused by, Aspergillus niger. In some embodiments, the fungus is, or the fungal infection is caused by, Aspergillus terreus. In some embodiments, the fungus is, or the fungal infection is caused by, Fusarium spp. In some embodiments, the fungus is, or the fungal infection is caused by, Fusarium solani. In some embodiments, the fungus is, or the fungal infection is caused by, Fusarium moniliforme. In some embodiments, the fungus is, or the fungal infection is caused by, Fusarium proliferatum. In some embodiments, the fungus is, or the fungal infection is caused by, Malassezia spp. In some embodiments, the fungus is, or the fungal infection is caused by, Malassezia pachydermatis. In some embodiments, the fungus is, or the fungal infection is caused by, a Mucorales. In some embodiments, the fungus is, or the fungal infection is caused by, Mucor spp. In some embodiments, the fungus is, or the fungal infection is caused by, M. circinelloides. In some embodiments, the fungus is, or the fungal infection is caused by, Rhizopus spp. In some embodiments, the fungus is, or the fungal infection is caused by, Rhizopus delemar. In some embodiments, the fungus is, or the fungal infection is caused by, Rhizopus oryzae. In some embodiments, the fungus is, or the fungal infection is caused by, Lichtheimia spp. In some embodiments, the fungus is, or the fungal infection is caused by, Lichtheimia corymbifera. In some embodiments, the fungus is, or the fungal infection is caused by, Rhizomucor spp. In some embodiments, the fungus is, or the fungal infection is caused by, Candida spp. In some embodiments, the fungus is, or the fungal infection is caused by, Candida albicans. In some embodiments, the fungus is, or the fungal infection is caused by, Candida glabrata. In some embodiments, the fungus is, or the fungal infection is caused by, Candida tropicalis. In some embodiments, the fungus is, or the fungal infection is caused by, Candida krusei. In some embodiments, the fungus is, or the fungal infection is caused by, Candida auris. In some embodiments, the fungus is, or the fungal infection is caused by, Cryptococcus spp. In some embodiments, the fungus is, or the fungal infection is caused by, Cryptococcus neoformans. In some embodiments, the fungus is, or the fungal infection is caused by, Chrysosporium parvum. In some embodiments, the fungus is, or the fungal infection is caused by, Metarhizium anisopliae. In some embodiments, the fungus is, or the fungal infection is caused Attorney Docket No. UAZ-43145.601 UA23-030 by, Phaeoisaria clematidis. In some embodiments, the fungus is, or the fungal infection is caused by Sarcopodium oculorum. Additional pathogenic fungi include the genus Candida (examples include C. albicans, C. glabrata, C. krusei, C. tropicalis, C. guilliermondii, C. parapsilosis, C. dubliniensis and C. auris), the genus Cryptococcus (examples include C. neoformans and C. gatti), the genus Trichosporon (examples include T. asahii, T. asteroides, T. cutaneum, T. dermatis, T. dohaense, T. inkin, T. loubieri, T. mucoides, and T. ovoides), the genus Malassezia (examples include M. globose and M. restricta), the genus Aspergillus (examples include A. fumigatus, A. flavus, A. terreus and A. niger), the genus Fusarium (examples include F. solani, F. falciforme, F. oxysporum, F. verticillioides, and F. proliferatum), the genus Mucor (examples include M. circinelloides, M. ramosissimus, M. indicus, M. rasemosus, and M. piriformis), the genus Blastomyces (examples include B. dermatitidis and B. brasiliensis), the genus Coccidioides (examples include C. immitis, and C. posadasii), the genus Pneumocystis (examples include P. carinii and P. jiroveci), the genus Histoplasma (examples include H. capsulatum), the genus Trichophyton (examples include T. schoenleinii, T. mentagrophytes, T. verrucosum, and T. rubrum), the genus Rhizopus (examples include R. oryzae and R. stolonifera), the genus Apophysomyces (examples include A. variabilis), the genus Rhizomucor (examples include R. pusillus, R. regularior, and R. chlamydosporus), the genus Lichtheimia (examples include L. ramose and L. corymbifera), the genus Scedosporium (examples include S. apiospermum), and the genus Lomentospora (examples include L. prolificans). In some embodiments, the fungi is Mucorales (for which conventional therapy results are poor), and other lethal pathogens for which current therapy is poor or lacking (Fusarium, Scedosporium, Lomentospora, Acremonium, and Exserohilum). In some embodiments, the fungal species is resistant to a therapeutic agent. In some embodiments, the fungal species is resistant to an azole. In some embodiments, the fungal species is resistant to an echinocandin. In some embodiments, the fungal species is CAS- resistant. In some embodiments, the fungal species is VOR-resistant. In certain embodiments, methods for treating or preventing a parasitic infection in a mammal are provided. In such embodiments, the method comprises administering to the mammal in need thereof a therapeutically effective amount of an ionic liquid formulation. In some embodiments, the mammal is a human being. In some embodiments, the mammal is a human being suffering from or at risk of suffering from a parasitic infection. In some Attorney Docket No. UAZ-43145.601 UA23-030 embodiments, the parasitic infection is selected from African trypanosomiasis, amoebiasis, ascariasis, babesiosis, Chagas disease, cryptosporidiosis, cutaneous larva migrans, dirofilariasis, echinococcosis, fasciolosis, filariasis, lymphatic filariasis, giardiasis, helminthiasis, hookworm infection, leishmaniasis, visceral leishmaniasis, malaria, neurocysticercosis, onchocerciasis, protozoan infection, schistosomiasis, taeniasis, tapeworm infection, toxocariasis, toxoplasmosis, trichinosis, and zoonosis. In some embodiments, the method further comprises administering to the mammal an antiparasitic agent. In some embodiments, the antiparasitic agent is an antiprotozoal, an antihelminthic, an antinematode, an anticestode, an antitrematode, an antiamoebic, or an antifungal. In some embodiments, the antiparasitic agent is selected from albendazole, amphotericin B, benznidazole, bephenium, diethylcarbamzine, eflornithine, flubendazole, ivermectin, mebendazole, meglumine antimonite, melarsoprol, metronidazole, miltefosine, niclosamide, nifurtimox, nitazoxanide, pentavalent antimony, praziquantel, pyrantel, pyrvinium, sodium stibogluconate, thiabendazole, and tinidazole. In certain embodiments, methods for treating or preventing neurocysticercosis in a mammal are provided. In such embodiments, the method comprises administering to the mammal in need thereof a therapeutically effective amount of an ionic liquid formulation. In some embodiments, the mammal is a human being. In some embodiments, the mammal is a human being suffering from or at risk of suffering from neurocysticercosis. In some embodiments, the method further comprises administering to the mammal an antiparasitic agent. In some embodiments, the antiparasitic agent is an antiprotozoal, an antihelminthic, an antinematode, an anticestode, an antitrematode, an antiamoebic, or an antifungal. In some embodiments, the antiparasitic agent is selected from albendazole, amphotericin B, benznidazole, bephenium, diethylcarbamzine, eflornithine, flubendazole, ivermectin, mebendazole, meglumine antimonite, melarsoprol, metronidazole, miltefosine, niclosamide, nifurtimox, nitazoxanide, pentavalent antimony, praziquantel, pyrantel, pyrvinium, sodium stibogluconate, thiabendazole, and tinidazole. In some embodiments, suitable dosage ranges for intravenous (i.v.) administration are 0.01 mg to 500 mg per kg body weight, 0.1 mg to 100 mg per kg body weight, 1 mg to 50 mg per kg body weight, or 10 mg to 35 mg per kg body weight. Suitable dosage ranges for other modes of administration can be calculated based on the forgoing dosages as known by those skilled in the art. For example, recommended dosages for intradermal, intramuscular, intraperitoneal, subcutaneous, epidural, sublingual, intracerebral, intravaginal, transdermal Attorney Docket No. UAZ-43145.601 UA23-030 administration or administration by inhalation are in the range of 0.001 mg to 200 mg per kg of body weight, 0.01 mg to 100 mg per kg of body weight, 0.1 mg to 50 mg per kg of body weight, or 1 mg to 20 mg per kg of body weight. Effective doses may be extrapolated from dose- response curves derived from in vitro or animal model test systems. Such animal models and systems are well known in the art. The ionic liquid formulations described herein can be administered in any conventional manner by any route where they are active. Administration can be systemic, topical, or oral. For example, administration can be, but is not limited to, parenteral, subcutaneous, intravenous, intramuscular, intraperitoneal, transdermal, oral, buccal, or ocular routes, or intravaginally, by inhalation, by depot injections, or by implants. Thus, modes of administration for the ionic liquid formulations described herein (either alone or in combination with other pharmaceuticals) can be, but are not limited to, sublingual, injectable (including short-acting, depot, implant and pellet forms injected subcutaneously or intramuscularly), or by use of vaginal creams, suppositories, pessaries, vaginal rings, rectal suppositories, intrauterine devices, and transdermal forms such as patches and creams. The selection of the specific route of administration and the dose regimen is to be adjusted or titrated by the clinician according to methods known to the clinician to obtain the desired clinical response. The amount of ionic liquid formulations described herein to be administered is that amount which is therapeutically effective. The dosage to be administered will depend on the characteristics of the subject being treated, e.g., the particular animal treated, age, weight, health, types of concurrent treatment, if any, and frequency of treatments, and can be easily determined by one of skill in the art (e.g., by the clinician). The amount of a ionic liquid formulations described herein that will be effective in the treatment and/or prevention of a fungal infection will depend on the nature of the fungal infection, and can be determined by standard clinical techniques. In addition, in vitro or in vivo assays may optionally be employed to help identify optimal dosage ranges. The precise dose to be employed in the compositions will also depend on the route of administration, and the seriousness of the fungal infection, and should be decided according to the judgment of the practitioner and each patient's circumstances. However, a suitable dosage range for oral administration is, generally, from about 0.001 milligram to about 200 milligrams per kilogram body weight. In some embodiments, the oral dose is from about 0.01 milligram to 100 milligrams per kilogram body weight, from about 0.01 milligram to about 70 milligrams per kilogram body weight, from about 0.1 milligram to about 50 milligrams per kilogram body weight, from 0.5 milligram to about 20 milligrams per Attorney Docket No. UAZ-43145.601 UA23-030 kilogram body weight, or from about 1 milligram to about 10 milligrams per kilogram body weight. In some embodiments, the oral dose is about 5 milligrams per kilogram body weight. It should be noted that the attending physician would know how to and when to terminate, interrupt, or adjust administration due to toxicity or organ dysfunctions. Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response were not adequate (precluding toxicity). The magnitude of an administrated dose in the management of the disorder of interest will vary with the severity of the symptoms to be treated and the route of administration. Further, the dose, and perhaps dose frequency, will also vary according to the age, body weight, and response of the individual patient. A program comparable to that discussed above may be used in veterinary medicine. 5. Kits In another aspect, the disclosure provides kits comprising at least one disclosed ionic liquid formulation, and instructions for using the ionic liquid formulation. The kits can also comprise other agents and/or products co-packaged, co-formulated, and/or co-delivered with other components. For example, a drug manufacturer, a drug reseller, a physician, a compounding shop, or a pharmacist can provide a kit comprising a disclosed ionic liquid formulation and/or product and another agent for delivery to a patient. The kits can also comprise instructions for using the components of the kit. The instructions are relevant materials or methodologies pertaining to the kit. The materials may include any combination of the following: background information, list of components, brief or detailed protocols for using the compositions, trouble-shooting, references, technical support, and any other related documents. Instructions can be supplied with the kit or as a separate member component, either as a paper form or an electronic form which may be supplied on computer readable memory device or downloaded from an internet website, or as recorded presentation. It is understood that the disclosed kits can be employed in connection with the disclosed methods. The kit may further contain containers or devices for use with the methods or compositions disclosed herein. The kits optionally may provide additional components such as buffers and disposable single-use equipment (e.g., pipettes, cell culture plates or flasks). The kits provided herein are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging, and the like. Individual member components of the kits may be physically packaged together or separately. Attorney Docket No. UAZ-43145.601 UA23-030 EXAMPLES The following examples are illustrative, but not limiting, of the ionic liquid formulations, and methods of the present invention. Other suitable modifications and adaptations of the variety of conditions and parameters normally encountered in clinical therapy and which are obvious to those skilled in the art are within the spirit and scope of the invention. The use of pronouns such as “I”, “we”, and “our”, for example, refer to one or more of the inventors. Example 1. Ionic Liquid Formulations Including Oxfendazole Oxfendazole (OXF) is the singular anthelmintic benzimidazole applicable for oral CM therapy. The anthelmintic benzimidazoles: albendazole (ABZ), mebendazole (MBZ), flubendazole (FBZ), triclabendazole (TCZ), fenbendazole (FNBZ), oxibendazole (OBZ), and oxfendazole (OXF) have broad-spectrum activity and are U.S. Food and Drug Administration (FDA)-approved for the treatment of various human and veterinary parasitic infections.^7-11 Previously reported in vitro studies^12-15, including our published paper¹⁶ and preliminary data (Table 1), showed that MBZ, FBZ, TCZ, FNBZ, and OXF are active against C. neoformans at nM to µM concentrations in vitro, indicating their potential to be repurposed for CM therapy whereas OBZ and thiabendazole are inactive against C. neoformans.¹³ However, there is a discrepancy between the in vitro and in vivo efficacy of anthelmintic benzimidazoles against C. neoformans, with previous studies showing minimal in vivo activity when ABZ, FBZ, or FNBZ were given orally.^14,15 Our preliminary oral pharmacokinetics (PK) studies on various anthelmintic benzimidazoles (20 mg/kg oral suspension) showed that only OXF attained plasma levels (Figure 1A) that were 4-fold greater than its IC₉₀ against C. neoformans (Figure 1B) whereas other anthelmintic benzimidazoles showed limited plasma exposure (< IC90 values). Our preliminary in vivo efficacy in CD-1 mice infected with C. neoformans showed that among various anthelmintic benzimidazoles, only OXF could significantly reduce the C. neoformans burden in the lungs (Figure 1C). Furthermore, oral OXF suspension showed significant in vivo efficacy and improved survival in the murine CM model (Figure 1D). However, the observed in vivo OXF efficacy is insufficient to completely prevent mortality indicating the need to improve the oral delivery and efficacy of OXF. Table 1: The anion used for the preparation of OXF-ILs impacts the solubility profile (n= 3; data expressed as mean). Attorney Docket No. UAZ-43145.601 UA23-030

Suboptimal physicochemical properties of OXF and lack of dose-proportional PK of OXF necessitate the development of improved oral formulations. Anthelmintic benzimidazoles including OXF are highly crystalline, hydrophobic drugs that are insoluble in lipids and have low and pH-dependent aqueous solubility (Figure 2). Our preliminary data show that the solubility of OXF declines from ~60 µg/mL at pH 1.2 (stomach pH) to ~ 5 µg/mL at pH 6.8 (intestinal pH). A recently conducted Phase I clinical trial demonstrated that oral OXF did not yield a dose-proportional increase in plasma levels^17,18 due to its limited and pH-dependent solubility indicating the need to improve oral delivery. The low or no solubility of OXF in organic and/or pharmaceutical solvents and lipids prohibits the development of various drug solubilization strategies and polymeric or lipid nanoformulations. To improve in vivo efficacy, a drug delivery strategy that expands the oral delivery, bioavailability, and tissue distribution of OXF (and many other drugs with similar problems) is imperative. Emerging applications of ionic liquids (ILs) indicated ILs as a next-generation translational drug delivery modality. ILs are low melting organic salts which can be liquid at room temperature.^19-22 ILs have been used as a solvent in chemical reactions for a long time but their drug delivery applications are still emerging. Recently, ILs were used as drug solubilizers and skin permeation enhancers,^19-22 leading to at least two IL-based products currently in clinical trials for dermal/transdermal delivery. However, transforming “difficult-to-deliver” ionizable drugs into drug-based amphiphilic ILs to achieve improved delivery is a strategy awaiting full- scale exploration. The synthesis of ionic liquids (ILs) with fatty counterions and their subsequent incorporation into oral lipid nanoemulsion improved the oral bioavailability of hydrophobic and weakly basic drugs such as itraconazole, lumefantrine, and cabozantinib.^23-25 However, these drugs are also amenable to various other solubilization strategies due to their solubility in organic solvents. The application of an IL strategy for the improved oral delivery of Attorney Docket No. UAZ-43145.601 UA23-030 highly crystalline, hydrophobic ionizable brick dust molecules such as anthelmintic benzimidazoles that are not amenable to other translational solubilization strategies remains unexplored. Using an in-situ salt synthesis approach followed by a salt metathesis reaction with an amphiphilic Generally Regarded As Safe (GRAS) anion such as sodium docusate, we successfully transformed anthelmintic benzimidazoles into amphiphilic drug-based ILs (Figure 3) with dramatically increased solubility in organic solvents and 30-fold higher solubility in lipids. Due to the high organic solvent solubility of docusate-based ILs, we can package them into polymeric nanoformulations such as SoluPlus nanomicelles (NM).¹⁶ Experiments were conducted to unravel the role of the counterion used for the synthesis of drug-based ILs, and the polymeric nanoformulation used for packaging of the IL, on the PK, biodistribution, and in vivo efficacy of ionizable hydrophobic drugs. The impact of the counterion used for the synthesis of drug-based ILs on the oral bioavailability, PK, and tissue penetration of drugs is currently unknown. Similarly, no information is available on the effect of the type of nanocarrier used for encapsulating drug-based ILs on their oral bioavailability, PK, and tissue penetration. The proposed work will address these fundamental gaps in knowledge regarding the impact of counterion and nanocarrier type on the in vivo fate of drug-based ILs, using OXF as an example. In parallel, our studies will develop first-in-class OXF-IL nanoformulation(s) for oral CM therapy to address the critical need for new drug treatments that target this human fungal pathogen responsible for high mortality. OXF is an innovative first-in-class anthelmintic benzimidazole for oral CM therapy. Our preliminary molecular docking data show that, compared to other anthelmintic benzimidazoles,¹⁶ OXF has a higher binding affinity (binding energy: -8.2 kcal/mol) to C. neoformans β-tubulin (modeled based on homology to the Saccharomyces cerevisiae β-tubulin sequence) compared to human β-tubulin (binding energy: -6.7 kcal/mol), indicating the possibility of fewer off-target effects. We validated the target engagement in a C. neoformans strain containing GFP-labeled β-tubulin. Our preliminary studies demonstrated that C. neoformans does not develop resistance to OXF (shown later in preliminary data). Finally, our in vivo studies demonstrated antifungal efficacy and survival upon treatment with oral OXF suspension in a mouse model of CM (Figures 1C and D). To our knowledge, this is the first evidence of an orally effective drug (OXF) that targets C. neoformans β-tubulin in vivo. Interestingly, recent Phase I clinical trials showed that oral OXF suspension is well tolerated in humans up to a 60 mg/kg dose with no signs of neurotoxicity (a typical side effect of drugs that Attorney Docket No. UAZ-43145.601 UA23-030 impact human β-tubulin).^{17,18, 26} Taken together, OXF is an unexplored and innovative first-in- class candidate for oral CM therapy. Nano-scale drug-based amphiphilic IL(s) as an innovative strategy for oral delivery of hydrophobic ionizable brick dust molecules including OXF. Brick dust molecules such as anthelmintic benzimidazoles including OXF have low solubility in organic solvents, water, and lipids,^17,27-31 and cannot be developed into amorphous solid dispersions or polymeric nanoformulations. The recently conducted Phase I trial on OXF highlights the limitations for the clinical development of OXF due to the lack of availability of appropriate formulations.¹⁷ We demonstrated that amphiphilic GRAS anions, such as sodium docusate can transform all anthelmintic benzimidazoles (including OXF) into amphiphilic docusate-based ILs with no crystallinity and improved solubility in organic solvents and lipids. For the first time, we demonstrated the ability of SoluPlus, a biodegradable self-assembling polymer suitable for oral delivery,^32,33 to package amphiphilic ILs with high loading capability to yield nanomicelles (NM)¹⁶ that can be delivered as an oral solution or can be freeze-dried to obtain a powder. We further showed that orally delivered SoluPlus NM containing oxfendazole docusate (OXF-Doc), an amphiphilic IL, resulted in significantly higher in vivo pharmacokinetics (PK), brain levels of OXF and in vivo efficacy in a murine CM model compared to pure OXF suspension. We have extended this strategy to deliver other brick dust molecules such as rilpivirine, and clofazimine indicating its potential as an overarching drug delivery strategy. Example 1A - The successful synthesis and characterization of oxfendazole docusate (OXF- Doc). Using the previously used procedure (Figure 3) with suitable modifications, we efficiently transformed OXF to OXF-Doc (yield > 90%) using sodium docusate and characterized OXF-Doc using various spectroscopic, chromatographic, and thermal techniques (Figure 4). We synthesized additional OXF-ILs (OXF oleate and OXF docosahexaenoate) using the procedure described in Figure 4 and we characterized them using similar techniques. Example 1B - Anthelmintic benzimidazoles and docusate-based ILs perturb microtubule assembly in Cryptococcus neoformans (Cn), and Cn does not develop resistance to OXF or OXF-Doc. To determine whether conversion of the anthelmintic benzimidazoles to docusate-based ILs affects their target, we validated that depolymerization of β-tubulin is equivalent between Attorney Docket No. UAZ-43145.601 UA23-030 albendazole (ABZ) and the IL, ABZ docusate (ABZ-Doc) (Figure 5).¹⁶ Previous in vitro studies suggested some species of fungi can develop resistance to the anthelminthic benzimidazoles which can impact their development as viable antifungal therapies.^13,15 To examine resistance, resilience, and tolerance, we monitored colony forming units (CFUs) following treatment with OXF or OXF-Doc at various time points (Figure 6). These data show no evidence of resistance and only minimal resilience and tolerance with OXF or OXF-Doc treatment. Thus, OXF is a viable therapeutic agent for Cn infection and the conversion of OXF into ILs is unlikely to alter the efficacy of OXF. Example 1C – GRAS counterions used for the synthesis of OXF-ILs show differential solubility. In addition to sodium docusate, we selected oleic acid, docosahexaenoic acid, cholic acid, acesulfame potassium, and saccharin sodium as GRAS anions to synthesize OXF-ILs (Figure 7 and Scheme 1). The selected GRAS anions have different chemical structures, unsaturation, chain length, acidity (pKa), and polarity/amphiphilicity and they all have been used to improve the solubility and/or permeability of hydrophobic drugs.^34-37 Using spectroscopic characterization, we confirmed the interaction between GRAS anions and OXF and the transformation of highly crystalline OXF into a soft pasty mass, with additional characterization ongoing. We determined the impact of the GRAS counterion on the solubility characteristics of OXF-ILs. As presented in Table 1, it is evident that the type of GRAS anion used for the synthesis of ILs impacts the solubility of OXF in water and buffers representing gastrointestinal pH. Further, unlike pure OXF, all the OXF-ILs showed significantly higher solubility (10-100 mg/ml) in organic solvents such as methanol, ethanol, and acetone, indicating excellent pharmaceutical processability. Scheme 1.

Example 1D - Amphiphilic ILs can be efficiently incorporated into SoluPlus nanomicelles (NM) to further improve their oral delivery. While the transformation of ionizable drugs with suboptimal solubility and permeability characteristics to amphiphilic IL(s) could improve their pharmaceutical processability, lipid Attorney Docket No. UAZ-43145.601 UA23-030 solubility, and permeability, packaging these ILs into nanoformulations could further improve the delivery, bioavailability, and efficacy of ILs. SoluPlus is a biodegradable amphiphilic copolymer, which forms nano-scale micelles upon dilution with physiological fluids and can encapsulate a variety of hydrophobic drugs, leading to improved solubility, permeability, and bioavailability.^32,33 We showed that amphiphilic docusate-based ILs of albendazole, mebendazole, and flubendazole can be stably encapsulated in SoluPlus NM.¹⁶ Similarly, we successfully packaged OXF-Doc into SoluPlus NM (Figure 8A) and confirmed the morphology of OXF-Doc-SoluPlus NM using TEM (Figure 8B). We also evaluated the effect of the OXF- Doc to SoluPlus ratio on the size and homogeneity (PDI) of micelles (Figure 8C). The developed OXF-Doc-SoluPlus NM retained their nanosize (< 80 nm) irrespective of the pH of the dispersion medium (Figure 8D). Our preliminary studies demonstrate that SoluPlus NM containing OXF-Doc can be efficiently freeze dried and readily reconstituted to yield nanomicelles with negligible size change. Example 1E – Oral OXF-Doc SoluPlus NM showed significant improvement in plasma, lung, and brain OXF levels compared to oral OXF suspension. In two separate experiments, we evaluated PK and biodistribution (lung and brain) of orally delivered OXF-Doc SoluPlus NM and OXF suspension (OXF dose: 20 mg/kg). Interestingly, OXF-Doc SoluPlus NM showed over 3-fold improvement in OXF plasma, lung, and brain levels and ~4-fold reduction in clearance compared to oral OXF suspension (Figure 9) indicating the importance of optimizing drug delivery using SoluPlus NM containing OXF-IL. Notably, the OXF-Doc SoluPlus NM resulted in OXF brain levels > IC90 of OXF but still lower than target OXF brain levels (2 X IC₉₀), indicating the need for further optimization of drug delivery. Example 1F – Once daily oral OXF-Doc-SoluPlus NM showed excellent tolerability after 14-day exposure. We evaluated the long-term safety of orally administered OXF-Doc-SoluPlus NM (OXF dose: 20 mg/kg), OXF suspension (OXF dose: 20 mg/kg), and blank SoluPlus micelles (vehicle control) compared to untreated healthy CD-1 mice CD-1 mice (n≥ 4/group; 50% females and 50% males) for 14 days. All OXF formulations were dosed once daily. All the treatments including OXF-Doc-SoluPlus NM were well tolerated for 14 days with no decline in the body weight (Figure 10) and no gross behavioral changes. No pathological changes in the vital organs Attorney Docket No. UAZ-43145.601 UA23-030 were observed. We also evaluated the liver function, kidney function, blood glucose, and various blood parameters including RBC count, WBC count, neutrophils, lymphocytes, platelets, and hemoglobin. A daily exposure of OXF-Doc-SoluPlus NM or OXF suspension for 14 days did not show any abnormal changes in the biochemical parameters as well as blood chemistry (Figure 11). Example 1G - Oral OXF-Doc-SoluPlus NM showed a dose-proportional in vivo antifungal efficacy in a mouse model of CM. A recently conducted Phase I clinical trial concluded that OXF’s clinical development could be hampered by the lack of dose-proportional systemic exposure after oral administration.¹⁷ Hence, we wanted to evaluate the potential of OXF-Doc-SoluPlus NM to overcome this limitation. Interestingly, OXF-Doc-SoluPlus NM showed a dose-proportional in vivo antifungal effect in a mouse model of CM compared to OXF suspension (Figure 12). Based on this study, we decided to evaluate the short-term and long-term efficacy of oral OXF-Doc- SoluPlus NM at an OXF dose of 20 mg/kg. Example 1H - Daily oral OXF-Doc-SoluPlus NM therapy showed 100% survival even after 75 days without visible side effects. CM patients often require long-term therapy. Hence, we evaluated the long-term survival of Cn-infected mice treated with oral OXF suspension or OXF-Doc SoluPlus NM (20 mg/kg OXF). Mice treated with daily oral OXF-Doc SoluPlus NM exhibited 100% survival (7/7) at day 75 (Figure 13A) and no visible signs of toxicity indicating good tolerability. In contrast, the OXF suspension was 37.5 % survival (3/8) at day 75, and mice in the untreated control group reached 100% mortality in 22 days (Figure 13A). At 75 days, the OXF-Doc SoluPlus NM- treated mice presented no gross toxicity but residual Cn burden was observed in 70% of mice (Figure 13B), indicating the need for further optimization of the dose of OXF-Doc-SoluPlus NM and/or formulation strategy. Example 1J – Evaluate the effect of counterion on the in vitro efficacy, pharmacokinetics (PK), and biodistribution of OXF-ILs. Our PK studies show that OXF suspension yielded brain levels below the intended target (2X IC₉₀). Hence, we hypothesize that the transformation of OXF to OXF-ILs will improve its PK and biodistribution and help achieve target OXF levels. Previous studies and our preliminary Attorney Docket No. UAZ-43145.601 UA23-030 data found that the GRAS counterion used for the synthesis of drug-based ILs can impact water and/or lipid solubility, in vitro cytocompatibility, and in vitro efficacy.^34-37 However, the impact of the counterion used for IL synthesis on the PK and biodistribution of drugs including OXF is unknown. To address this knowledge gap, we have prepared various OXF-ILs (Figure 7, Scheme 1) with differential solubility characteristics (Table 1) using GRAS anions with variable amphiphilicity and anionic functional groups. We will evaluate the impact of the GRAS anions used for the OXF-IL synthesis on the in vitro antifungal activity, PK, and biodistribution of OXF. These experiments will allow us to identify the OXF-IL(s) that could be moved toward preclinical development. We already synthesized OXF docusate, OXF oleate, OXF docosahexaenoate, OXF saccharinate, and OXF acesulfame. We will synthesize OXF tocopherol phosphate using the salt metathesis method shown in Figure 4. We will characterize the OXF-ILs using FT-IR spectroscopy, ¹H NMR, ¹³C NMR, MS, HPLC, DSC, and powder X-ray diffraction (PXRD) as described previously.¹⁶ While anthelmintic benzimidazoles, including OXF, are active against Cn in vitro, the presence of a GRAS anion as a counterion in OXF-ILs could enhance or reduce their antifungal activity. Hence, the impact of the GRAS anions on the OXF-IL antifungal activity will be determined. To evaluate the effect of the anions on the in vitro efficacy of already generated OXF- ILs, we will perform in vitro antifungal susceptibility on the lab reference strain (KN99α), the fluconazole susceptible clinical strain (UgCl395), and a fluconazole-resistant clinical strain (ASTRO635), in biological triplicate, using the EUCAST broth microdilution method to determine IC₅₀ and IC₉₀ values, as described in our previous paper.¹⁶ As in Table 2, our preliminary in vitro minimum inhibitory concentration (MIC) assays using both KN99α and UgCl395 showed enhanced antifungal activity of the OXF-Doc, but a decrease in MIC was observed for the oleate-based IL. These data highlight the need to screen all the OXF-ILs to comprehend how various GRAS anions impact the in vitro activity of OXF. To determine whether the various OXF-ILs exhibit differences in antifungal activity due to resistance, resilience, or tolerance, we will perform in vitro resistance/tolerance assays as described in Figure 6. The already generated OXF-ILs will be tested using the three Cn strains with variable fluconazole resistance (KN99α, UgCl395, ASTRO635). These studies will evaluate the effect of the GRAS anions on the development of resistance/tolerance in vitro. Cn is known to develop high tolerance and resistance towards fluconazole and low tolerance and minimal resistance to Attorney Docket No. UAZ-43145.601 UA23-030 amphotericin B.^38,39 Thus, assays with these two drugs will be used as controls to determine the relative impact of the various ILs on the development of tolerance and resistance to OXF. Table 2. In vitro activity of OXF, and its docusate/oleate ILs (n= 3; data expressed as mean). nterion on the PK and

biodistribution of OXF-ILs. This aim will be the first step toward addressing the gap in knowledge about the impact of counterion used for the IL synthesis on the in vivo fate of hydrophobic ionizable drugs with high crystallinity. The information gathered in this aim will be valuable for the drug-based IL field and will also identify the OXF-IL(s) that can yield the target OXF lung and brain levels (2X IC90; ~1.5 µg/g) for a prolonged period to elicit the therapeutic response in the murine CM model. A summary of PK experiments is provided in Figure 14. The PK and biodistribution studies will be performed in healthy CD-1 mice, a typical mouse background for Cn antifungal drug studies. We will evaluate the PK and biodistribution of OXF suspension in hydroxypropyl methylcellulose (HPMC), OXF-Doc, and 5 additional OXF-ILs (see Figure 7, Scheme 1) uniformly suspended/solubilized in HPMC dispersion. Briefly, six- to eight-week-old CD-1 mice will be randomly divided into groups of 60 [n=10 mice (5 males and 5 females) per time point/group] and the mice will be treated with 20 mg/kg of OXF suspension, or OXF-IL suspension/solution in HPMC (equivalent to 20 mg/kg OXF) via 100 µl oral gavage. Blood will be collected, and organs (lungs, kidney, liver, and brain) will be harvested at 0.25, 0.5, 1, 2, 4, 8, and 24 h. Blood will be centrifuged at 2000 g and 4°C for 15 min and the recovered plasma, and tissues (lungs, kidney, liver, spleen, and brain) will be perfused and stored at -20°C until further analysis. The concentration of OXF in plasma, lung, liver, kidney, spleen, and brain tissue homogenates will be determined using LC-MS/MS. The PK of OXF in plasma, lungs, liver, kidney, and brain tissues will be calculated using WinNonlin software. Example 1K – Develop polymeric and lipid nanoformulations containing OXF-ILs and evaluate their impact on the PK and biodistribution of OXF-ILs. Attorney Docket No. UAZ-43145.601 UA23-030 Our PK studies on OXF-Doc-SoluPlus NM (Figure 9) and in vivo efficacy studies on OXF-Doc-SoluPlus NM (Figure 12) showed that encapsulation of docusate-based ILs in SoluPlus NM improved their in vivo performance compared to pure drug indicating the importance of packaging ILs in a nanoformulation. These studies identified OXF-Doc-SoluPlus NM (polymeric nanoformulation) as the first OXF nanoformulation “hit” that needs further optimization. However, the impact of the encapsulation of drug-based ILs containing different counterions into the polymeric nanocarrier such as SoluPlus NM on the PK, and biodistribution of ILs of hydrophobic ionizable drugs such as OXF has never been carried out. The studies proposed in this aim will address this gap in the knowledge that is critical for the advancement of the field. In parallel, we will identify the three lead OXF-IL SoluPlus NM formulations that achieve target OXF levels in the brain that can advance for preclinical safety and efficacy. Our preliminary in vivo efficacy studies established the importance of packaging OXF-IL into SoluPlus nanomicelles to overcome the pH-dependent solubility of OXF/OXF-IL (Table 1 and Figure 8D) leading to improved oral delivery (Figure 9) and in vivo antifungal efficacy (Figures 12 and 13). Similarly, it is important to evaluate the feasibility of packaging OXF-ILs synthesized SoluPlus NM. Our pilot studies (Table 3) show that the synthesized OXF-ILs can be packaged into SoluPlus NM and that the counterion used for OXF-IL synthesis influences the resulting size of the NM. However, further optimization and characterization are needed. Table 3. Preliminary data showing SoluPlus NM can encapsulate various OXF-ILs

We will use the solvent-antisolvent method or thin film hydration method to evaluate the feasibility of encapsulating the OXF-ILs into SoluPlus nanomicelles using different weight ratios of OXF-IL and SoluPlus (outlined in Scheme 2).^16,33 The SoluPlus nanomicelles will be characterized for micelle size, homogeneity (polydispersity index), surface charge, physical stability for at least 24 hours (h), and OXF encapsulation efficiency using centrifugal filtration followed by analysis of OXF using the HPLC method. Scheme 2. Schematic of the development of SoluPlus nanomicelles (NM) containing OXF- IL(s) Attorney Docket No. UAZ-43145.601 UA23-030

optimized SoluPlus NM containing OXF-IL will be diluted with biorelevant buffers such as simulated gastric and intestinal fluid to evaluate the effect of gastrointestinal pH on the micelle size and stability. The optimized SoluPlus NM containing OXF-IL will be freeze dried to obtain a powder and the effect of freeze drying on the size, homogeneity, and surface charge will be evaluated. The freeze dried SoluPlus NM containing OXF-ILs will be used for long-term stability testing, PK studies, safety evaluation, and in vivo efficacy studies. As previous studies show that SoluPlus can inhibit the precipitation of drugs in the gastrointestinal tract,³² we will also evaluate the ability of the SoluPlus NM containing OXF-ILs to prevent the precipitation of OXF in fasted-state and fed-state simulated intestinal fluid (FaSSIF and FeSSIF). Experiments will be conducted to evaluate PK and biodistribution of SoluPlus NM containing OXF-ILs. This aim addresses a major knowledge gap on the impact of the encapsulation of the drug-based IL into polymeric nanocarriers such as SoluPlus NM and the counterion used for the synthesis of drug-based IL on the PK and biodistribution of drugs. This information is critical to identifying the optimal drug-based IL and the nanoformulation strategy for OXF and many more drugs. This aim will also identify three lead OXF-IL SoluPlus NM compositions that can yield the target OXF lung and brain levels (2X IC90; ~1.5 µg/g) to elicit the therapeutic response in the murine CM model. Additionally, OXF showed a lack of dose- proportional PK in the Phase I clinical trial, ^17,18 but our OXF-Doc-SoluPlus NM showed dose- proportional in vivo efficacy (see Figure 12). The evaluation of dose-dependent PK and biodistribution is the first step in drug development before proceeding to the in vivo efficacy studies. Hence, we will evaluate the ability of SoluPlus NM containing OXF-IL(s) to demonstrate dose proportionality in terms of PK and biodistribution. A summary of PK experiments is provided in Figure 15. Briefly, six- to eight-week-old CD-1 mice will be randomly divided into groups of 60 [n=10 mice (5 males and 5 females) per time point/group] and the mice will be treated with 20 mg/kg of OXF suspension, SoluPlus NM containing OXF-IL (maximum 6 formulations; 20 mg/kg OXF) via 100µl oral gavage. Mice will be euthanized at 0.5, 1, 2, 4, 8, and 24 h to collect blood and harvest the lungs, kidney, liver, spleen, and brain. The three lead OXF-IL SoluPlus NM nanoformulations that exhibit the best PK and biodistribution (plasma, lung, and brain OXF levels ≥ 1.5 µg/g) from the studies Attorney Docket No. UAZ-43145.601 UA23-030 described in Figure 15, will be orally delivered as above at doses ranging from 10, 20, 30, and 40 mg/kg of OXF to determine dose proportionality in PK and biodistribution. Example 1L – Evaluate the long-term safety and in vivo efficacy of the lead OXF-IL nanoformulations in a mouse model of CM, alone and in combination with existing antifungal drug treatments CM in patients manifests as latent pulmonary infection in healthy individuals but disseminates to the bloodstream and ultimately enters the CNS to cause CM in immunocompromised individuals. Because the initial pulmonary infection is ubiquitous, immunocompromised patients are often treated prophylactically, when Cn antigen is detected in the bloodstream indicating dissemination, or when patients present with CM.⁴¹ Current CM treatment involves a short initial treatment with high toxicity amphotericin B and flucytosine, followed by a 3-12 month consolidation treatment phase with fluconazole.⁴¹ To define the in vivo safety and efficacy of the SoluPlus NM containing OXF-IL(s), we will perform studies in mice that recapitulate the progression of human disease. Experiments will be conducted to evaluate the long-term in vivo safety of nanoformulations containing OXF-IL. Immunocompromised individuals often require long-term prophylactic or therapeutic intervention to prevent/treat CM.⁴¹ While pure OXF suspension is shown to be safe in rats and humans at doses up to 30-60 mg/kg,^17,18,42 the OXF-IL nanoformulations can significantly improve plasma and tissue exposure of OXF (see Figure 9). While daily administration of SoluPlus NM containing OXF-Doc (20 mg/kg OXF) did not show any gross adverse effects for 14 days (Figure 11), evaluation of the long-term safety of OXF-IL SoluPlus NM is warranted. The top three nanoformulations containing OXF-IL, and OXF suspension as a control, will be evaluated in long-term safety studies. Briefly, the various OXF formulations will be orally administered at 20 mg/kg, 30 mg/kg, and 60 mg/kg (doses well tolerated in Phase I clinical trials in humans) every day for three months and the groups of ten 6-8-week-old CD-1 mice will be monitored for body weight, blood chemistry, immunogenicity (immunoglobulins and cytokines) cardiovascular, renal, hepatic, and neurological toxicity. Mice will be euthanized at 900 days and histopathology (H&E stain) will be performed on the lungs, brain, kidneys, heart, and liver. Experiments will be conducted to evaluate the in vivo efficacy of nanoformulations containing OXF-ILs in a mouse model of CM. For in vivo efficacy studies, we will carry out two Attorney Docket No. UAZ-43145.601 UA23-030 variations of the mouse CM model^43-46 (Fig.17). First, we will use a typical drug pre-treatment regimen commonly used for antifungal drug efficacy testing (Fig.17A). Briefly, CD-1 mice will be intranasally infected with 5x10⁴ KN99α and treated daily by oral gavage starting at day -1 with 20 mg/kg OXF suspension, OXF-IL (maximum 2;, three lead OXF nanoformulations, and a combination of flucytosine (5-FC; 250 mg/kg daily) and 5 mg/kg amphotericin B (Fungizone; route of administration: i.p.) as a positive control. Mice will be sacrificed on days 14, 21, and their natural endpoint. Determinants of the natural endpoint are 20% total weight loss, 1 g/day weight loss for two consecutive days, or neurological symptoms including loss of sternal recumbency, partial paralysis, seizure, convulsion, or coma.^43-46 CFUs in the lungs and brain will be analyzed to compare the ability of the drug formulations to control fungal growth in the lungs, dissemination to, and growth within the brain. A second variation of the experiment will mimic typical clinical drug use in patients with CM disease presentation where the fungus has already disseminated to the brain (Fig.17B). In these experiments, drug treatment is initiated on day 14 post-infection, with fungal dissemination to the brain typically detected at day 7 and mortality in the absence of effective drug treatment occurring by day 25.⁴⁴ Mice will be euthanized at day 21 and their natural endpoint (see above for determinants). CFUs in the lungs and brain will be analyzed to compare the ability of the drug formulations to control or eradicate a pre-existing disseminated infection. In both experimental variations, the concentration of OXF in the plasma, lung, and brain will be analyzed using LC-MS/MS on days 14, 21, and the natural endpoint. Five mice per treatment group will be used for CFU and drug-level analyses and 10 mice will be used to monitor survival (natural endpoint). Experiments will be conducted to evaluate in vitro synergy and in vivo efficacy of combination therapy with existing antifungal drug treatments. Our preliminary data show that OXF-Doc- SoluPlus NM was able to effectively prevent mortality, but viable Cn was present in many of the mice at 75 days post-infection, suggesting that combination therapy approaches may improve fungal clearance. We will perform in vitro checkerboard MIC assays with two commonly utilized oral antifungals–fluconazole and 5-flucytosine (5-FC)–to determine additive or synergistic drug-drug interactions with the OXF suspension, OXF-IL, and OXF-IL-SoluPlus NM containing OXF-IL. In humans and the mouse model, both fluconazole and 5-FC are ineffective when used in monotherapy, but enhance the efficacy of intravenously administered amphotericin B. We will evaluate the prophylactic (early treatment model) and therapeutic (late treatment model) activity (Figure 17) of OXF suspension or nanoformulations of OXF-IL (OXF dose: 20 mg/kg) in combination with commercial oral fluconazole formulation (20 mg/kg twice Attorney Docket No. UAZ-43145.601 UA23-030 daily) or commercial 5-flucytosine (250 mg/kg) to determine the ability of combination therapy to improve oral CM therapy. A combination of i.p. amphotericin B and 5-flucytosine will be used as a positive control. Five mice per treatment group will be used for CFU and drug level analyses at 14 days, 21 days, and natural endpoint; 10 mice will be used to monitor survival (natural endpoint). INCORPORATION BY REFERENCE The entire disclosure of each of the patent documents and scientific articles referred to herein is incorporated by reference for all purposes. The following references are herein incorporated by reference in their entireties: 1. Mourad, A.; Perfect, J. R. Present and future therapy of cryptococcus infections. J Fungi. 2018; 4: 79. 2. Rajasingham, R.; Smith, R. M.; Park, B. J.; Jarvis, J. N.; Govender, N. P.; Chiller, T. M.; Denning, D. W.; Loyse, A.; Boulware, D. R. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis.2017; 17: 873-881. 3. Montoya, M. C.; DiDone, L.; Heier, R. F.; Meyers, M. J.; Krysan, D. J. Antifungal Phenothiazines: optimization, characterization of mechanism, and modulation of neuroreceptor activity. ACS infect Dis.2017; 4: 499-507. 4. Iyer KR, Revie NM, Fu C, Robbins N, Cowen LE. Treatment strategies for cryptococcal infection: challenges, advances and future outlook. Nat Rev Microbiol. 2021 Jul;19(7):454- 466. 5. Hurt WJ, Harrison TS, Molloy SF, Bicanic TA. Combination Therapy for HIV-Associated Cryptococcal Meningitis-A Success Story. J Fungi (Basel).2021 Dec 20;7(12):1098. 6. Spadari, C. d. C.; Wirth, F.; Lopes, L. B.; Ishida, K. New Approaches for Cryptococcosis Treatment. Microorganisms.2020; 8, 613. 7. Mkupasi EM, Sikasunge CS, Ngowi HA, Johansen MV. Efficacy and safety of anthelmintics tested against Taenia solium cysticercosis in pigs. PLoS Negl Trop Dis. 2013 Jul 25;7(7):e2200. 8. Partridge FA, Forman R, Bataille CJR, Wynne GM, Nick M, Russell AJ, Else KJ, Sattelle DB. Anthelmintic drug discovery: target identification, screening methods and the role of open science. Beilstein J Org Chem.2020 Jun 2;16:1203-1224. 9. Del Brutto OH. Current approaches to cysticidal drug therapy for neurocysticercosis. Expert Rev Anti Infect Ther.2020 Aug;18(8):789-798. 10. Gokbulut C, McKellar QA. Anthelmintic drugs used in equine species. Vet Parasitol. 2018 Sep 15;261:27-52. 11. Gonzalez AE, Codd EE, Horton J, Garcia HH, Gilman RH. Oxfendazole: a promising agent for the treatment and control of helminth infections in humans. Expert Rev Anti Infect Ther. 2019 Jan;17(1):51-56. 12. Cruz, M.; Bartlett, M.; Edlind, T. In vitro susceptibility of the opportunistic fungus Cryptococcus neoformans to anthelmintic benzimidazoles. Antimicrob Agents Chemother. 1994; 38, 378-380. 13. Joffe, L. S.; Schneider, R.; Lopes, W.; Azevedo, R.; Staats, C. C.; Kmetzsch, L.; Schrank, A.; Del Poeta, M.; Vainstein, M. H.; Rodrigues, M. L. The anti-helminthic compound mebendazole has multiple antifungal effects against Cryptococcus neoformans. Front Microbiol.2017; 8, 535. Attorney Docket No. UAZ-43145.601 UA23-030 14. Nixon, G. L.; McEntee, L.; Johnson, A.; Farrington, N.; Whalley, S.; Livermore, J.; Natal, C.; Washbourn, G.; Bibby, J.; Berry, N. Repurposing and reformulation of the antiparasitic agent flubendazole for treatment of cryptococcal meningoencephalitis, a neglected fungal disease. Antimicrob Agents Chemother.2018; 62, e01909-17. 15. de Oliveira, H. C.; Joffe, L. S.; Simon, K. S.; Castelli, R. F.; Reis, F. C.; Bryan, A. M.; Borges, B. S.; Medeiros, L. C. S.; Bocca, A. L.; Del Poeta, M. Fenbendazole Controls In Vitro Growth, Virulence Potential, and Animal Infection in the Cryptococcus Model. Antimicrob Agents Chemother.2020; 64 , e00286-20. 16. Sutar Y., Fulton S., Paul S., Mhatre S., Altamirano S., Saeed H.K., Patel P., Bhat S., Mallick S., Chauhan H., Patravale V.B., Nielsen K., Date A.A., Docusate-based ionic liquids of anthelmintic benzimidazoles show improved pharmaceutical processability, lipid solubility, and in vitro activity against Cryptococcus neoformans. ACS Infectious Diseases, 2021, 7:2637-2649. 17. An G, Murry DJ, Gajurel K, Bach T, Deye G, Stebounova LV, Codd EE, Horton J, Gonzalez AE, Garcia HH, Ince D, Hodgson-Zingman D, Nomicos EYH, Conrad T, Kennedy J, Jones W, Gilman RH, Winokur P. Pharmacokinetics, safety, and tolerability of oxfendazole in healthy volunteers: a randomized, placebo-controlled first-in-human single-dose escalation study. Antimicrob Agents Chemother.2019 Mar 27;63(4):e02255-18. 18. Bach T, Galbiati S, Kennedy JK, Deye G, Nomicos EYH, Codd EE, Garcia HH, Horton J, Gilman RH, Gonzalez AE, Winokur P, An G. Pharmacokinetics, safety, and tolerability of oxfendazole in healthy adults in an open-label phase 1 multiple ascending dose and food effect study. Antimicrob Agents Chemother.2020 Oct 20;64(11):e01018-20. 19. Shamshina JL, Rogers RD. Ionic Liquids: New Forms of Active Pharmaceutical Ingredients with Unique, Tunable Properties. Chem Rev.2023 Oct 25;123(20):11894-11953 20. Shamshina, J. L.; Rogers, R. D. Are Myths and Preconceptions Preventing us from Applying Ionic Liquid Forms of Antiviral Medicines to the Current Health Crisis? Int J Mol Sci.2020; 21, 6002. 21. Williams HD, Ford L, Igonin A, Shan Z, Botti P, Morgen MM, Hu G, Pouton CW, Scammells PJ, Porter CJH, Benameur H. Unlocking the full potential of lipid-based formulations using lipophilic salt/ionic liquid forms. Adv Drug Deliv Rev. 2019 Mar 1;142:75-90. 22. Moshikur RM, Carrier RL, Moniruzzaman M, Goto M. Recent Advances in Biocompatible Ionic Liquids in Drug Formulation and Delivery. Pharmaceutics.2023 Apr 7;15(4):1179. 23. Tay E, Nguyen TH, Ford L, Williams HD, Benameur H, Scammells PJ, Porter CJH. Ionic Liquid forms of the antimalarial lumefantrine in combination with LFCS Type IIIB lipid- based formulations preferentially increase lipid solubility, in vitro solubilization behavior and in vivo exposure. Pharmaceutics.2019 Dec 22;12(1):17. 24. Sahbaz Y, Williams HD, Nguyen TH, Saunders J, Ford L, Charman SA, Scammells PJ, Porter CJ. Transformation of poorly water-soluble drugs into lipophilic ionic liquids enhances oral drug exposure from lipid-based formulations. Mol Pharm. 2015 Jun 1;12(6):1980-91. 25. Williams HD, Ford L, Han S, Tangso KJ, Lim S, Shackleford DM, Vodak DT, Benameur H, Pouton CW, Scammells PJ, Porter CJH. Enhancing the oral absorption of kinase inhibitors using lipophilic salts and lipid-based formulations. Mol Pharm. 2018 Dec 3;15(12):5678- 5696. 26. Bach T, Murry DJ, Stebounova LV, Deye G, Winokur P, An G. Population pharmacokinetic model of oxfendazole and metabolites in healthy adults following single ascending doses. Antimicrob Agents Chemother.2021 Mar 18;65(4):e02129-20. 27. Pettarin, M.; Bolger, M. B.; Chronowska, M.; Kostewicz, E. S. A combined in vitro in-silico approach to predict the oral bioavailability of borderline BCS Class II/IV weak base Attorney Docket No. UAZ-43145.601 UA23-030 albendazole and its main metabolite albendazole sulfoxide. Eur J Pharm Sci. 2020; 55, 105552. 28. Kourentas A, Vertzoni M, Khadra I, Symillides M, Clark H, Halbert G, Butler J, Reppas C. Evaluation of the impact of excipients and an albendazole salt on albendazole concentrations in upper small intestine using an in vitro biorelevant gastrointestinal transfer (BioGIT) system. J Pharm Sci.2016 Sep;105(9):2896-2903. 29. Mukherjee T, Plakogiannis FM. Development and oral bioavailability assessment of a supersaturated self-microemulsifying drug delivery system (SMEDDS) of albendazole. J Pharm Pharmacol.2010 Sep;62(9):1112-20. 30. Rao MRP, Chaudhari J, Trotta F, Caldera F. Investigation of Cyclodextrin-Based Nanosponges for Solubility and Bioavailability Enhancement of Rilpivirine. AAPS PharmSciTech.2018 Jul;19(5):2358-2369. 31. Yamanouchi K, Ishimaru T, Kakuno T, Takemoto Y, Kawatsu S, Kondo K, Maruyama M, Higaki K. Improvement and characterization of oral absorption behavior of clofazimine by SNEDDS: Quantitative evaluation of extensive lymphatic transport. Eur J Pharm Biopharm. 2023 Jun;187:141-155. 32. Linn M, Collnot EM, Djuric D, Hempel K, Fabian E, Kolter K, Lehr CM. Soluplus® as an effective absorption enhancer of poorly soluble drugs in vitro and in vivo. Eur J Pharm Sci. 2012 Feb 14;45(3):336-43. 33. Jin X, Zhou B, Xue L, San W. Soluplus(®) micelles as a potential drug delivery system for reversal of resistant tumor. Biomed Pharmacother.2015 Feb;69:388-95. 34. Saeed HK, Sutar Y, Patel P, Bhat R, Mallick S, Hatada AE, Koomoa DT, Lange I, Date AA. Synthesis and Characterization of Lipophilic Salts of Metformin to Improve Its Repurposing for Cancer Therapy. ACS Omega.2021, 6:2626-2637. 35. Whitehead K, Karr N, Mitragotri S. Safe and effective permeation enhancers for oral drug delivery. Pharm Res.2008 Aug;25(8):1782-8. 36. Mooranian A, Negrulj R, Mathavan S, Martinez J, Sciarretta J, Chen-Tan N, Mukkur TK, Mikov M, Lalic-Popovic M, Stojancevic M, Golocorbin-Kon S, Al-Salami H. An advanced microencapsulated system: a platform for optimized oral delivery of antidiabetic drug-bile acid formulations. Pharm Dev Technol.2015;20(6):702-9. 37. da Costa NF, Santos IA, Fernandes AI, Pinto JF. Sulfonic Acid Derivatives in the Production of Stable Co-Amorphous Systems for Solubility Enhancement. J Pharm Sci. 2022 Dec;111(12):3327-3339. 38. Venkateswarlu K, Taylor M, Manning NJ, Rinaldi MG, Kelly SL. Fluconazole tolerance in clinical isolates of Cryptococcus neoformans. Antimicrob Agents Chemother. 1997 Apr;41(4):748-51. 39. Bosch C, Toplis B, Vreulink JM, Volschenk H, Botha A. Nitrogen concentration affects amphotericin B and fluconazole tolerance of pathogenic cryptococci. FEMS Yeast Res.2020 Mar 1;20(2):foaa010. 40. Gerlach ES, Altamirano S, Yoder JM, Luggya TS, Akampurira A, Meya DB, Boulware DR, Rhein J, Nielsen K. ATI-2307 exhibits equivalent antifungal activity in Cryptococcus neoformans clinical isolates with high and low fluconazole IC50. Front Cell Infect Microbiol.2021, 11:695240. 41. Altamirano S, Jackson KM, Nielsen K. The interplay of phenotype and genotype in Cryptococcus neoformans disease. Biosci Rep.2020 Oct 30;40(10):BSR20190337. 42. Codd EE, Ng HH, McFarlane C, Riccio ES, Doppalapudi R, Mirsalis JC, Horton RJ, Gonzalez AE, Garcia HH, Gilman RH; Cysticercosis Working Group in Peru. Preclinical studies on the pharmacokinetics, safety, and toxicology of oxfendazole: toward first in human studies. Int J Toxicol.2015 Mar-Apr;34(2):129-37. Attorney Docket No. UAZ-43145.601 UA23-030 43. Mukaremera L, McDonald TR, Nielsen JN, Molenaar CJ, Akampurira A, Schutz C, Taseera K, Muzoora C, Meintjes G, Meya DB, Boulware DR, Nielsen K. The mouse inhalation model of Cryptococcus neoformans infection recapitulates strain virulence in humans and shows that closely related strains can possess differential virulence. Infect Immun. 2019, 87:e00046-19. 44. Nielsen K, Cox GM, Litvintseva AP, Mylonakis E, Malliaris SD, Benjamin DK Jr, Giles SS, Mitchell TG, Casadevall A, Perfect JR, Heitman J. Cryptococcus neoformans {alpha} strains preferentially disseminate to the central nervous system during coinfection. Infect Immun. 2005, 73:4922-33. 45. Crabtree JN, Okagaki LH, Wiesner DL, Strain AK, Nielsen JN, Nielsen K. Titan cell production enhances the virulence of Cryptococcus neoformans. Infect Immun. 2012, 80:3776-85. 46. Gerstein AC, Jackson KM, McDonald TR, Wang Y, Lueck BD, Bohjanen S, Smith KD, Akampurira A, Meya DB, Xue C, Boulware DR, Nielsen K. Identification of pathogen genomic differences that impact human immune response and disease during Cryptococcus neoformans infection. mBio.2019, 10:e01440-19. 47. Sabiiti W, May RC, Pursall ER. Experimental models of cryptococcosis. Int J Microbiol. 2012;2012:626745. 48. Czerniak R. Gender-based differences in pharmacokinetics in laboratory animal models. Int J Toxicol.2001 May-Jun;20(3):161-3. 49. Lortholary, O., Improvisi, L., Fitting, C., Cavaillon, J. M. & Dromer, F. Influence of gender and age on course of infection and cytokine responses in mice with disseminated 50. Cryptococcus neoformans infection. Clin Microbiol Infect 8, 31-37. 51. Crabtree JN, Okagaki LH, Wiesner DL, Strain AK, Nielsen JN, Nielsen K. Titan cell production enhances the virulence of Cryptococcus neoformans. Infect Immun. 2012 Nov;80(11):3776-85. EQUIVALENTS The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Claims

Attorney Docket No. UAZ-43145.601 UA23-030 What Is Claimed Is: 1. A composition comprising an ionic liquid formulation comprising: a) a protonated compound encompassed within the following Formula I:

component; wherein R1, R2, and the anionic moieties that render the

formulation a liquid at room temperature; wherein R1, R2, and the anionic component chemical moieties that render the formulation with a melting point less than 100 degree C; wherein R1, R2, and the anionic component chemical moieties that render the formulation as an amphiphilic liquid; wherein R1, R2, and the anionic component chemical moieties that render the formulation a non-crystalline form; wherein R1, R2, and the anionic component chemical moieties that render the formulation as therapeutically effective agent for treating a condition or disease known to be treatable with OXF; wherein R1, R2, and the anionic component chemical moieties that render the formulation as having therapeutically effective antifungal activity; wherein R1, R2, and the anionic component chemical moieties that render the formulation as having therapeutically effective antifungal activity against Cryptococcus neoformans; wherein R1, R2, and the anionic component chemical moieties that render the formulation as therapeutically effective agent for perturbing microtubule assembly in Cryptococcus neoformans; wherein R1, R2, and the anionic component chemical moieties that render the formulation as therapeutically effective agent for treating fungal disorders; wherein R1, R2, and the anionic component chemical moieties that render the formulation as therapeutically effective agent for treating Cryptococcal meningitis (CM); wherein R1, R2, and the anionic component chemical moieties that render the formulation as therapeutically effective agent for treating human neurocysticercosis wherein R1, R2, and the anionic component chemical moieties that render the formulation as having enhanced bioavailability of the compound encompassed within Formula I; wherein R1, R2, and the anionic component chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated within) with biodegradable Attorney Docket No. UAZ-43145.601 UA23-030 polymers; wherein R1, R2, and the anionic component chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated within) with biodegradable polymers thereby enhancing bioavailabity of the ionic liquid formulation; wherein R1, R2, and the anionic component chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated within) with lipid nanoemulsions; and wherein R1, R2, and the anionic component chemical moieties that render the formulation capable of association (e.g., packaging; encapsulated within) with nanomicelles (e.g., SoluPlus nanomicelles) (e.g., lipid nanoemulsions). O 2. The composition of claim 1, (substituted or unsubstituted).

3. The composition of claim 1, wherein R2 is substituted or unsubstituted (C1-C6) alkyl (e.g., CH₃). 4. The composition of claim 1, wherein the anionic component is selected from an anionic therapeutic agent, an anionic amino acid, an anionic nutraceutical, an anionic agrochemical molecule, an anionic functional food, an anionic excipient, and a pharmaceutically acceptable anion. 5. The composition of claim 1, wherein the anionic component is an anionic carboxylate, an anionic sulfonate, an anionic sulfate, an anionic phosphate, an anionic phosphonate, an anionic sulfamate, or a chemical moiety having negatively charged functional group.

Attorney Docket No. UAZ-43145.601 UA23-030 6. The composition of claim 1, wherein the anionic component is .

7. The composition of claim 1, wherein the anionic component is a bile acid selected from cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, lithocholic acid, glycocholic acid, taurocholic acid, and tauroursodeoxycholic acid. 8. The composition of claim 1, wherein the anionic component is selected from: .

9. The composition of claim 1, wherein the anionic component is an anionic carboxylate molecule selected from one of the following: , ,

, , Attorney Docket No. UAZ-43145.601 UA23-030 ,

.

10. The composition of claim 1, wherein the anionic component is a negatively charged functional group selected from: butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, palmitic acid, undecylenic acid, oleic acid, linoleic acid, linolenic acid, myristoleic acid, ricinoleic acid, elaidic acid, N-decanoyl sarcosine, Lauryl sarcosine, docosahexaenoic acid, biotin, lactobionic acid, eicosapentaenoic acid, nervonic acid, Vitamin E succinate, 4- phenylbutyric acid, pamoic acid, α-lipoic acid, ibuprofen, naproxen, squalene acid, cholesterol hemisuccinate, capric acid, salcaprozic acid, docusic acid, cholic acid, glycocholic acid, taurocholic acid, tauroursodeoxycholic acid and other anionic bile acids, taurine, camphor sulfonic acid lauryl sulfate, cholesterol sulfate, DOPA, vitamin E phosphate, thiamine phosphate, saccharine sodium, acesulfame potassium, cyclamate sodium, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, gallic acid, vanillic acid, and phthalic acid. 11. The composition of claim 1, wherein the anionic component is an anionic carboxylate molecule selected from one of the following: ,

, , Attorney Docket No. UAZ-43145.601 UA23-030 ,

12. The composition of claim 1, wherein the anionic component is selected from a saturated fatty acid derivative moiety (carboxylate), an unsaturated fatty acid derivative moiety, an aromatic acid derivative moiety, a sulfonate derivative moiety, a sulfate derivative moiety, a phosphate derivative moiety, and a sulfamate derivative moiety. 13. The composition of claim 1, wherein the anionic component is selected from a negatively charged functional group of saturated fatty acids selected from butyric acid (butanoic acid), caproic acid (hexanoic acid), caprylic acid (octanoic acid), capric acid (decanoic acid)lauric acid (dodecanoic acid), palmitic acid (hexadecenoic acid), and cholic acid. 14. The composition of claim 1, wherein the anionic component is selected from a negatively charged functional group of unsaturated fatty acids selected from: undecylenic acid, oleic acid, linoleic acid, docosahexaenoic acid, eicosapentaenoic acid, nervonic acid, myristoleic acid, elaidic acid, and ricinoleic acid. Attorney Docket No. UAZ-43145.601 UA23-030 15. The composition of claim 1, wherein the anionic component is selected from a negatively charged functional group of aromatic acids selected from: salcaprozic acid, α- tocopherol succinate, 4-phenyl butyric acid, Ibuprofen, Naproxen, pamoic acid, Dolutegravir, Cabotegravir, and Bictegravir. 16. The composition of claim 1, wherein the anionic component is selected from a negatively charged functional group of sulfonate anions selected from: docusic acid, camphor sulfonic acid, taurocholic acid, tauroursodeoxycholic acid, and taurine. 17. The composition of claim 1, wherein the anionic component is selected from a negatively charged functional group of sulfate anions selected from: lauryl sulfate, and cholesterol sulfate. 18. The composition of claim 1, wherein the anionic component is selected from a negatively charged functional group of a phosphate anion selected from: α-tocopherol phosphate, 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA), and thiamine phosphate. 19. The composition of claim 1, wherein the anionic component is selected from a negatively charged functional group of sulfamate anions selected from: acesulfame, saccharin, and cyclamate.

Attorney Docket No. UAZ-43145.601 UA23-030 20. The composition of claim 1, wherein the anionic component is selected from: .

Attorney Docket No. UAZ-43145.601 UA23-030 21. The composition of claim 1, wherein the anionic component is selected from a fatty ),

Attorney Docket No. UAZ-43145.601 UA23-030

22. The composition of claim 1, wherein the protonated compound and anionic component are present in a ratio in the range of about 5:1 to about 1:5. 23. The composition of claim 1, wherein the ionic liquid formulation is a lipid nanoemulsion. 24. The composition of claim 1, wherein the ionic liquid formulation is associated with (e.g., encapsulated within) a nanoformulation. 25. The composition of claim 1, wherein the ionic liquid formulation is associated with (e.g., encapsulated within) a polymeric nanoformulation. 26. The composition of claim 1, wherein the ionic liquid formulation is associated with (e.g., encapsulated within) a nanomicelle (e.g., SoluPlus nanomicelle). 27. The composition of claim 23, wherein the ionic liquid formulation is associated with (e.g., encapsulated within) nanoformulations. 28. The composition of claim 23, wherein the ionic liquid formulation is associated with (e.g., encapsulated within) polymeric nanoformulations. Attorney Docket No. UAZ-43145.601 UA23-030 29. The composition of claim 23, wherein the ionic liquid formulation is associated with (e.g., encapsulated within) nanomicelles (e.g., SoluPlus nanomicelles). 30. A pharmaceutical composition comprising an effective amount of a composition of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 31. The pharmaceutical composition of claim 30, wherein the composition further comprises at least one additional therapeutic agent. 32. The pharmaceutical composition of claim 31, wherein the at least one additional therapeutic agent comprises any type or kind of therapeutic agent capable of inhibiting fungal activity. 33. The pharmaceutical composition of claim 31, wherein the at least one additional therapeutic agent is selected from the following: a polyene, imidazole, triazole, thiazole, allylamine, echinocandin, among others. Examples include Amphotericin B, Candicidin, Filipin, Hamycin, Natamycin, Nystatin, Rimocidin, Bifonazole, Butoconazole, Clotrimazole, econazole, fenticonazole, isoconazole, kentoconazole, miconazole, omoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, albaconazole, fluconazole, isavuconazole, itraconazole, posaconazole, ravuconazole, terconazole, voriconazole, abafungin, amorolfin, butenafine, naftifine, terbinafine, anidulafungin, caspofungin, micafungin, benzoic acid, ciclopirox, flucytosine, griseofulvin, haloprogin, polygodial, tolnaftate, undecylenic acid, and crystal violet. 34. A method of treating or preventing a fungal infection in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of one or more of the compositions or pharmaceutical compositions recited in Claims 1-33. 35. The method of claim 34, wherein the mammal is a human being. 36. The method of claim 34, wherein the mammal is a human being suffering from or at risk of suffering from a fungal infection. Attorney Docket No. UAZ-43145.601 UA23-030 37. The method of claim 34, wherein the fungal infection is an Aspergillus spp., Fusarium spp., Malassezia spp., Candida spp., or Cryptococcus spp. infection. 38. The method of claim 34, wherein the fungal infection is an Aspergillus spp. infection. 39. The method of claim 38, wherein the Aspergillus spp. infection is selected from an Aspergillus fumigatus infection, an Aspergillus favus infection, an Aspergillus niger infection, an Aspergillus terreus infection. 40. The method of claim 34, wherein the fungal infection is a Fusarium spp. infection. 41. The method of claim 40, wherein the Fusarium spp. infection is selected from a Fusarium solani infection, a Fusarium moniliforme infection, and a Fusarium proliferatum infection. 42. The method of claim 34, wherein the fungal infection is an Malassezia spp. infection. 43. The method of claim 42, wherein the Malassezia spp. infection is a Malassezia pachydermatis infection. 44. The method of claim 34, wherein the fungal infection is a Candida spp. infection. 45. The method of claim 34, wherein the Candida spp. infection is selected from a Candida albicans infection, a Candida glabrata infection, a Candida tropicalis infection, a Candida krusei infection, and a Candida auris infection. 46. The method of claim 34, wherein the fungal infection is a Cryptococcus spp. infection. 47. The method of claim 46, wherein the Cryptococcus spp. infection is a Cryptococcus neoformans infection. 48. The method of claim 34, wherein the fungal infection is a Chrysosporium parvum, Attorney Docket No. UAZ-43145.601 UA23-030 Metarhizium anisopliae, Phaeoisaria clematidis, or Sarcopodium oculorum infection. 49. The method of claim 34, wherein the fungal infection is a Mucorales infection. 50. The method of claim 49, wherein the Mucorales infection is a Mucor spp., Rhizopus spp., Lichtheimia spp., or Rhizomucor spp. infection. 51. The method of claim 50, wherein the Mucor spp. infection is a M. circinelloides infection; wherein the Rhizopus spp. infection is a Rhizopus delemar infection or a Rhizopus oryzae infection; wherein the Lichtheimia spp. infection is a Lichtheimia corymbifera infection. 52. The method of claim 34, further comprising administering to the mammal in need thereof at least one additional therapeutic agent capable of inhibiting fungal activity. 53. The method of claim 52, wherein the at least one additional therapeutic agent is selected from the following: a polyene, imidazole, triazole, thiazole, allylamine, echinocandin, among others. Examples include Amphotericin B, Candicidin, Filipin, Hamycin, Natamycin, Nystatin, Rimocidin, Bifonazole, Butoconazole, Clotrimazole, econazole, fenticonazole, isoconazole, kentoconazole, miconazole, omoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, albaconazole, fluconazole, isavuconazole, itraconazole, posaconazole, ravuconazole, terconazole, voriconazole, abafungin, amorolfin, butenafine, naftifine, terbinafine, anidulafungin, caspofungin, micafungin, benzoic acid, ciclopirox, flucytosine, griseofulvin, haloprogin, polygodial, tolnaftate, undecylenic acid, and crystal violet. 54. A method of killing or inhibiting the growth of a fungus comprising contacting the fungus with a therapeutically effective amount of one or more of the compounds or pharmaceutical compositions recited in Claims 1-33. 55. The method of claim 54, wherein the fungus is selected from Aspergillus spp., Fusarium spp., Malassezia spp., Candida spp., or Cryptococcus spp.. Attorney Docket No. UAZ-43145.601 UA23-030 56. The method of claim 54, wherein the fungus is selected from Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Fusarium solani, Fusarium moniliforme, Fusarium proliferatum, Malassezia pachydermatis, Candida albicans, Candida glabrata infection, Candida tropicalis, Candida krusei, Candida auris, Cryptococcus neoformans, Chrysosporium parvum, Metarhizium anisopliae, Phaeoisaria clematidis, Sarcopodium oculorum, M. circinelloides, Rhizopus delemar, Rhizopus oryzae, and Lichtheimia corymbifera. 57. Use of a composition of any one of claims 1-33, or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment or prevention of a fungal infection. 58. The use of claim 57, wherein the fungal infection is related to one or more of: Aspergillus spp., Fusarium spp., Malassezia spp., Candida spp., and Cryptococcus spp.. 59. The use of claim 57, wherein the fungal infection is related to one or more of: Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Fusarium solani, Fusarium moniliforme, Fusarium proliferatum, Malassezia pachydermatis, Candida albicans, Candida glabrata infection, Candida tropicalis, Candida krusei, Candida auris, Cryptococcus neoformans, Chrysosporium parvum, Metarhizium anisopliae, Phaeoisaria clematidis, Sarcopodium oculorum, M. circinelloides, Rhizopus delemar, Rhizopus oryzae, and Lichtheimia corymbifera. 60. A method of treating or preventing a parasitic infection in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of one or more of the compositions or pharmaceutical compositions recited in Claims 1-33. 61. The method of claim 60, wherein the mammal is a human being. 62. The method of claim 60, wherein the mammal is a human being suffering from or at risk of suffering from a parasitic infection. 63. The method of claim 60, wherein the parasitic infection is selected from African trypanosomiasis, amoebiasis, ascariasis, babesiosis, Chagas disease, cryptosporidiosis, Attorney Docket No. UAZ-43145.601 UA23-030 cutaneous larva migrans, dirofilariasis, echinococcosis, fasciolosis, filariasis, lymphatic filariasis, giardiasis, helminthiasis, hookworm infection, leishmaniasis, visceral leishmaniasis, malaria, neurocysticercosis, onchocerciasis, protozoan infection, schistosomiasis, taeniasis, tapeworm infection, toxocariasis, toxoplasmosis, trichinosis, and zoonosis. 64. The method of Claim 60, further comprising administering to the mammal an antiparasitic agent. 65. The method of Claim 64, wherein the antiparasitic agent is an antiprotozoal, an antihelminthic, an antinematode, an anticestode, an antitrematode, an antiamoebic, or an antifungal. 66. The method of Claim 64, wherein the antiparasitic agent is selected from albendazole, amphotericin B, benznidazole, bephenium, diethylcarbamzine, eflornithine, flubendazole, ivermectin, mebendazole, meglumine antimonite, melarsoprol, metronidazole, miltefosine, niclosamide, nifurtimox, nitazoxanide, pentavalent antimony, praziquantel, pyrantel, pyrvinium, sodium stibogluconate, thiabendazole, and tinidazole. 67. A method of treating or preventing neurocysticercosis in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of one or more of the compositions or pharmaceutical compositions recited in Claims 1-33. 68. The method of claim 67, wherein the mammal is a human being. 69. The method of claim 67, wherein the mammal is a human being suffering from or at risk of suffering from neurocysticercosis. 70. The method of Claim 67, further comprising administering to the mammal an antiparasitic agent. 71. The method of Claim 70, wherein the antiparasitic agent is an antiprotozoal, an antihelminthic, an antinematode, an anticestode, an antitrematode, an antiamoebic, or an antifungal. Attorney Docket No. UAZ-43145.601 UA23-030 72. The method of Claim 70, wherein the antiparasitic agent is selected from albendazole, amphotericin B, benznidazole, bephenium, diethylcarbamzine, eflornithine, flubendazole, ivermectin, mebendazole, meglumine antimonite, melarsoprol, metronidazole, miltefosine, niclosamide, nifurtimox, nitazoxanide, pentavalent antimony, praziquantel, pyrantel, pyrvinium, sodium stibogluconate, thiabendazole, and tinidazole.