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WO2014165582A1 - Articles et procédés liés à l'administration transdermique d'un agent thérapeutique - Google Patents

Articles et procédés liés à l'administration transdermique d'un agent thérapeutique Download PDF

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Publication number
WO2014165582A1
WO2014165582A1 PCT/US2014/032662 US2014032662W WO2014165582A1 WO 2014165582 A1 WO2014165582 A1 WO 2014165582A1 US 2014032662 W US2014032662 W US 2014032662W WO 2014165582 A1 WO2014165582 A1 WO 2014165582A1
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WO
WIPO (PCT)
Prior art keywords
porous material
another aspect
loaded
article
weight
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2014/032662
Other languages
English (en)
Inventor
Andrew Penman
Eugenia P. KHARLAMPIEVA
Timothy M. Wick
Carlos Arturo CARMONA-MORAN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
UAB Research Foundation
Southern Research Institute
Original Assignee
UAB Research Foundation
Southern Research Institute
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by UAB Research Foundation, Southern Research Institute filed Critical UAB Research Foundation
Publication of WO2014165582A1 publication Critical patent/WO2014165582A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches

Definitions

  • Transdermal drug delivery devices are well known in the pharmaceutical arts as a method for delivering a wide variety of drugs, such as nitroglycerin, estradiol, testosterone, fentanyl, and clonidine.
  • Transdermal drug delivery devices typically involve a carrier (such as a liquid, gel, or solid matrix, or a mechanically sensitive adhesive) into which the drug to be delivered is incorporated. Because the skin presents a substantial barrier to ingress of foreign substances into the body, it is often desirable to incorporate excipients, such as penetration enhancers, into the carrier that enhance the rate at which the drug passes through the skin.
  • an article comprising: a) a first stimuli-responsive porous material, wherein the first stimuli-responsive porous material has a first and second side opposite from each other; b) a therapeutic agent; and c) a support material.
  • Also disclosed herein is a method of treating a disorder comprising application of an article disclosed herein to a subject in need of treatment of the disorder.
  • FIG. 1 shows a non-limiting ; configuration of the articles described herein.
  • FIG. 2 shows a non-limiting ; configuration of the articles described herein.
  • FIG. 3 shows a non-limiting ; configuration of the articles described herein.
  • FIG. 4 shows a non-limiting ; configuration of the articles described herein.
  • FIG. 5 shows a non-limiting ; configuration of the articles described herein.
  • FIG. 6 shows a non-limiting ; configuration of the articles described herein.
  • the article of figure 1 is incorporated in figure 6.
  • FIG. 7 shows a non-limiting configuration of the articles described herein.
  • the article of figure 1 is incorporated in figure 7.
  • Ranges can be expressed herein as from “about” one particular value, and/or to "about” another particular value. When such a range is expressed, a further aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about,” it will be understood that the particular value forms a further aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as "about” that particular value in addition to the value itself. For example, if the value "10” is disclosed, then “about 10" is also disclosed. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 1 1, 12, 13, and 14 are also disclosed.
  • a weight percent (wt. %) of a component is based on the total weight of the formulation or composition or material, in which the component is included.
  • X and Y are present at a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are contained in the composition.
  • the term "subject" refers to the target of administration, e.g. an animal.
  • the subject of the herein disclosed methods can be a vertebrate, such as a mammal, a fish, a bird, a reptile, or an amphibian.
  • the subject of the herein disclosed methods can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, fish, bird, or rodent.
  • the term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be covered.
  • the subject is a mammal.
  • a patient refers to a subject afflicted with a disease or disorder.
  • the term "patient” includes human and veterinary subjects.
  • the subject has been diagnosed with a need for treatment of one or more muscle disorders prior to the administering step.
  • the subject has been diagnosed with a need for treatment of osteoarthritis prior to the administering step.
  • treatment refers to the medical management of a patient with the intent to cure, ameliorate, stabilize, or prevent a disease, pathological condition, or disorder.
  • This term includes the use of disclosed articles as means for delivering therapeutic agents.
  • This term includes active treatment, that is, treatment directed specifically toward the improvement of a disease, pathological condition, or disorder, and also includes causal treatment, that is, treatment directed toward removal of the cause of the associated disease, pathological condition, or disorder.
  • this term includes palliative treatment, that is, treatment designed for the relief of symptoms rather than the curing of the disease, pathological condition, or disorder; preventative treatment, that is, treatment directed to minimizing or partially or completely inhibiting the development of the associated disease, pathological condition, or disorder; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the associated disease, pathological condition, or disorder.
  • the term covers any treatment of a subject, including a mammal (e.g., a human), and includes: (i) preventing the disease from occurring in a subject that can be predisposed to the disease but has not yet been diagnosed as having it; (ii) inhibiting the disease, i.e., arresting its development; (iii) relieving the disease, i.e., causing regression of the disease; or (iv) relieving symptoms of the disease, i.e., relieving pain caused by the disease.
  • the subject is a mammal such as a primate, and, in a further aspect, the subject is a human.
  • prevent refers to precluding, averting, obviating, forestalling, stopping, or hindering something from happening, especially by advance action. It is understood that where reduce, inhibit or prevent are used herein, unless specifically indicated otherwise, the use of the other two words is also expressly disclosed.
  • the term “diagnosed” means having been subjected to a physical examination by a person of skill, for example, a physician, and found to have a condition that can be diagnosed or treated by the compounds, compositions, or methods disclosed herein.
  • diagnosisd with osteoarthritis means having been subjected to a physical examination by a person of skill, for example, a physician, and found to have a condition that can be diagnosed or treated by a compound or composition that can treat or prevent osteoarthritis.
  • the phrase "identified to be in need of treatment for a disorder,” or the like refers to selection of a subject based upon need for treatment of the disorder.
  • a subject can be identified as having a need for treatment of a disorder (e.g., a disorder related to a microbial infection) based upon an earlier diagnosis by a person of skill and thereafter subjected to treatment for the disorder. It is contemplated that the identification can, in one aspect, be performed by a person different from the person making the diagnosis. It is also contemplated, in a further aspect, that the administration can be performed by one who subsequently performed the administration.
  • a disorder e.g., a disorder related to a microbial infection
  • administering refers to any method of providing a pharmaceutical preparation to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intravaginal administration, ophthalmic administration, intraaural administration, intracerebral administration, rectal administration, sublingual administration, buccal administration, and parenteral administration, including injectable such as intravenous administration, intra-arterial administration, intramuscular administration, and subcutaneous administration. Administration can be continuous or intermittent. In one aspect, administering is transdermal administration. In various aspects, a preparation can be administered therapeutically; that is, administered to treat an existing disease or condition. In further various aspects, a preparation can be administered prophylactically; that is, administered for prevention of a disease or condition.
  • the terms “effective amount” and “amount effective” refer to an amount that is sufficient to achieve the desired result or to have an effect on an undesired condition.
  • a “therapeutically effective amount” refers to an amount that is sufficient to achieve the desired therapeutic result or to have an effect on undesired symptoms, but is generally insufficient to cause adverse side effects.
  • the specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration; the route of administration; the rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed and like factors well known in the medical arts. For example, it is well within the skill of the art to start doses of a compound at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. If desired, the effective daily dose can be divided into multiple doses for purposes of administration.
  • compositions can contain such amounts or submultiples thereof to make up the daily dose.
  • the dosage can be adjusted by the individual physician in the event of any contraindications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products.
  • a preparation can be administered in a "prophylactically effective amount"; that is, an amount effective for prevention of a disease or condition.
  • pharmaceutically acceptable describes a material that is not biologically or otherwise undesirable, i.e., without causing an unacceptable level of undesirable biological effects or interacting in a deleterious manner.
  • the term "pharmaceutically acceptable carrier” refers to sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use.
  • suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like),
  • carboxymethylcellulose and suitable mixtures thereof vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate.
  • Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants.
  • These compositions can also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid and the like. It can also be desirable to include isotonic agents such as sugars, sodium chloride and the like.
  • Prolonged absorption of the injectable pharmaceutical form can be brought about by the inclusion of agents, such as aluminum monostearate and gelatin, which delay absorption.
  • injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide, poly(orthoesters) and
  • Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues.
  • the injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use.
  • Suitable inert carriers can include sugars such as lactose.
  • at least 95% by weight of the particles of the active ingredient have an effective particle size in the range of 0.01 to 10 micrometers.
  • compositions of the invention Disclosed are the components to be used to prepare the compositions of the invention as well as the compositions themselves to be used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds cannot be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular compound is disclosed and discussed and a number of modifications that can be made to a number of molecules including the compounds are discussed, specifically contemplated is each and every combination and permutation of the compound and the modifications that are possible unless specifically indicated to the contrary.
  • a "porous material,” for example a stimuli-responsive porous material, or the like terms refer to a material that has a large enough free volume space to accommodate a second composition, such as a composition comprising a therapeutic agent.
  • a material can have a free volume range from 40% to 99%.
  • the term "stimuli-responsive porous material” or the like terms refer to a material that changes one or more properties according to the environment they are in.
  • a stimuli-responsive porous material can change the one or more properties due to changes in one or more factors including, but not limited to temperature, mechanical load of the material, humidity, pH, light intensity, electrical field, or magnetic field.
  • the change of the one or more properties is drastic and discontinuous at a particular point of the one or more factors and results in release of cargo upon response.
  • a "thermo-responsive porous material” is a material that exhibits a drastic and discontinuous change of its physical property at a particular temperature or temperature range.
  • thermo-responsive porous materials have a lower critical solution temperature (LCST) at which thethermo-responsive porous materials change from being soluble in a given solvent to being insoluble in a given solvent.
  • the solvent can be water.
  • poly(N-vinylcaprolactam) has a LCST of 36 °C when the solvent is water.
  • the thermo-responsive material can have a LCST from 27 °C to 40 °C.
  • the thermo-responsive material can have a LCST from 32 °C to 40 °C.
  • thermo-responsive material can have a LCST from 32 °C to 38 °C. In yet another aspect, the thermo-responsive material can have a LCST from 32 °C to 46 °C.
  • a "mechanically-responsive porous material” is a material that exhibits a drastic and discontinuous change of its physical property with the force applied to the material. The change of property can be the ability of material to retain a substance, such as a composition comprising a therapeutic agent, inside the material.
  • a lower critical force is applied to the material a substance located within the mechanically -responsive porous material is released.
  • gellan gum and alginate are examples of mechanically -responsive porous materials.
  • compositions disclosed herein have certain functions.
  • the articles disclosed herein are useful for transdermal delivery of therapeutic agents.
  • the article can be a transdermal delivery article.
  • the article can be configured to achieve local delivery of the therapeutic agent.
  • the article can be configured in various sizes to fit a desired area of a body, such as, for example, a finger joint, a toe joint, a shoulder, a knee, an elbow, or an ankle joint.
  • an article comprising: a) a first stimuli-responsive porous material, wherein the first stimuli-responsive porous material has a first and second side opposite from each other; b) a therapeutic agent; and c) a support material.
  • the article further comprises a second stimuli-responsive porous material.
  • the article further comprises one or more penetration enhancers.
  • the article further comprises an adhesive material.
  • the adhesive material is present on the support material.
  • the adhesive material is present on the second side of the first stimuli-responsive porous material.
  • the article further comprises a matrix material.
  • the matrix material can be a stimuli-responsive porous material, for example a stimuli-responsive porous matrix material.
  • the matrix material can be loaded with a therapeutic agent.
  • the matrix material can be loaded with a penetration enhancer.
  • the matrix can be loaded with a penetration enhancer and a therapeutic agent.
  • the penetration enhancer can comprise one or more substances.
  • the article comprises one or more formulations comprising a therapeutic agent and one or more penetration enhancers.
  • the formulation can be fast acting and/or provide sustained release of the therapeutic agent.
  • An article with a fast acting formulation can deliver a therapeutically effective amount of a therapeutic agent within 10, 15, 20, 25, 30, 45, or 60 minutes after application of the article.
  • An article with a sustained release formulation can deliver a therapeutically effective amount of a therapeutic agent for at least 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12, hrs, 18 hrs, or 24 hrs.
  • the article can comprise two or more formulations.
  • the article can comprise two or more formulations comprising the same therapeutic agent but with different penetration enhancers.
  • Such article can, thus, can comprise a fast acting formulation and a sustained release formulation.
  • the different formulations can be present at different location or in different materials in the article.
  • a fast acting formulation can be present in a first stimuli-responsive porous material and the sustained release formulation can be present in a second stimuli-responsive porous material and/or in the matrix material.
  • the fast acting formulation and the sustained release formulation are physically and chemically separated from each other.
  • the fast acting formulation and the sustained release formulation can be physically separated by a barrier, such as a matrix material.
  • An article comprising both a fast acting formulation and a sustained release formulation can provide both fast and sustained of the therapeutic agent, thereby, providing immediate and long-term relief for a subject using the article.
  • the article can comprise two or more formulations comprising different therapeutic agents.
  • the different therapeutic agents can be in the same class of therapeutic agents, such as, for example, in the class of non-steroidal anti-inflammatory drugs (NSAID).
  • the different therapeutic agents can also be in different classes of therapeutic agents, such as for example, an NSAID and an anesthetic agent.
  • the article would then provide two different benefits to a subject, such as a human, upon application of the article. For example, upon application of such article comprising both an NSAID and an anesthetic agent to an inflamed area, the article would provide both pain relief and anti-inflammatory relief to the subject.
  • the two or more formulations comprising different therapeutic agents can be present at different location or in different materials in the article.
  • one formulation can be present in a first stimuli-responsive porous material and the second formulation can be present in a second stimuli-responsive porous material and/or in the matrix material.
  • the two or more formulations are physically and chemically separated from each other.
  • the two or more formulations can be physically separated by a barrier, such as a matrix material.
  • the article can comprise three or more formulations comprising different therapeutic agents.
  • the different therapeutic agents can be in the same class of therapeutic agents, such as, for example, in the class of non-steroidal anti-inflammatory drugs (NSAID).
  • Two of the different therapeutic agents can be in the same class of therapeutic agents, such as, for example, in the class of non-steroidal anti-inflammatory drugs (NSAID), and one of the therapeutic agents could be in a different class of therapeutic agents, such as, for example, an anesthetic agent.
  • the different therapeutic agents can also be in different classes of therapeutic agents, such as for example, an NSAID, an anesthetic agent, and an antibiotic agent.
  • the article could then provide multiple, such as two or three, different benefits to a subject, such as a human, upon application of the article.
  • the three or more formulations comprising different therapeutic agents can be present at different location or in different materials in the article.
  • one formulation can be present in a first stimuli- responsive porous material
  • the second formulation can be present in a second stimuli- responsive porous material
  • the third formulation can be present in the matrix material.
  • the three or more formulations are physically and chemically separated from each other.
  • the three or more formulations can be physically separated by a barrier, such as a matrix material.
  • the article is configured to conform to the shape of a body part. In another aspect, the article is configured to conform to the shape of a body where a joint is present.
  • the joint is the distal interphalangeal joint (DIP).
  • the joint is the basilar joint of the thumb (trapezium) and/or the first three bones of the thumb (metacarpal).
  • the joint is the metatarsophalangeal joint.
  • the joint is a finger joint, a toe joint, an ankle, an elbow, a wrist, a shoulder or a knee.
  • the article has the shape of a hollow tube.
  • the hollow tube can be fitted to a body part, such as the DIP.
  • the support material extends beyond the first stimuli-responsive porous material. In another aspect, the support material extends beyond the first stimuli-responsive porous material and the second stimuli-responsive porous material.
  • the support material is flexible. In another aspect, the support material is elastic. In yet another aspect, the support material is attached to the first side of the first stimuli- responsive porous material.
  • the article comprises a matrix material.
  • the matrix material comprises a matrix material, wherein the matrix material is attached to the support material.
  • the matrix material is configured on the support material to form one or more wells.
  • the first thermo-responsive and/or mechanically-responsive material is present in the one or more wells.
  • the matrix material is present between the first side of the stimuli-responsive porous material and the support material.
  • the first stimuli-responsive porous material and the second stimuli-responsive porous material are present in different wells.
  • the therapeutic agent is present in the one or more wells.
  • the therapeutic agent is present between the first side of the first stimuli- responsive porous material and the support material.
  • the first side of the first stimuli-responsive porous material is attached to the support material.
  • first side of the first stimuli-responsive porous material and the second stimuli-response material is attached to the support material.
  • first side of the first stimuli- responsive porous material is attached to the second stimuli-response material.
  • the article is configured so that the first stimuli-responsive porous material will be in contact with skin upon use of the article.
  • the article is configured so that the therapeutic agent is present between the first stimuli-response porous material and the support material. In one aspect, the article is configured so that the therapeutic agent is in contact with and is present between the first stimuli-response porous material and the support material.
  • the article is configured so that the porous matrix material loaded with a therapeutic agent is present between the first stimuli-response porous material and the support material. In one aspect, the article is configured so that the porous matrix material loaded with a therapeutic agent is in contact with and is present between the first stimuli-response porous material and the support material.
  • the article is configured so that the porous matrix material loaded with a therapeutic agent and one or more penetration enhancers is present between the first stimuli- response porous material and the support material. In one aspect, the article is configured so that the porous matrix material loaded with a therapeutic agent and one or more penetration enhancers is in contact with and is present between the first stimuli-response porous material and the support material.
  • the article is configured so that the first stimuli-responsive porous material and the support material are in contact. In one aspect, the article is configured so that the first stimuli-responsive porous material loaded with the therapeutic agent and the support material are in contact. In one aspect, the article is configured so that the first stimuli-responsive porous material loaded with the therapeutic agent and one or more penetration enhancers and the support material are in contact.
  • the article is configured so that one or more discrete areas of the article comprise the first stimuli-responsive porous material, and wherein the article comprises an adhesive material.
  • the article comprises at least 2, 5, 10, 15, 20, 25, 30, 35, 50, 100, 200, 500, 1,000, 5,000, 10,000, or 20,000 discrete areas.
  • FIG 6 shows an article with 24 discrete areas.
  • FIG. 1 shows article (100) with a support material (102), the support material (102) comprises a flexible fabric (104), such as a flexible hydrophobic fabric, and a backing membrane (106).
  • the flexible fabric (104), such as a flexible hydrophobic fabric, and the backing membrane (106) are attached to each other.
  • a matrix material (108) is attached to the support material (102), for example, the matrix material (108) is attached to the flexible fabric (104).
  • the matrix material (108) can be configured on the support material (102) to provide wells in the article (100).
  • an adhesive material (110) is present and attached to the support material (102), for example, the adhesive material (110) is attached to the flexible fabric (104).
  • the adhesive material (110) is present and attached to the matrix material (108).
  • a first stimuli-responsive porous material (112) is in contact with the matrix material (108), which can be configured to provide wells.
  • the first stimuli-responsive porous material (112) in one aspect, is present in the wells of the matrix material (108).
  • FIG. 2 shows article (200) with a support material (202), the support material (202) comprises a flexible fabric (204), such as a flexible hydrophobic fabric, and a backing membrane (206).
  • the flexible fabric (204), such as a flexible hydrophobic fabric, and the backing membrane (206) are attached to each other.
  • a therapeutic agent (208) is in contact with the support material (102), for example, therapeutic agent (208) is in contact with the flexible fabric (204).
  • an adhesive material (210) is present and attached to the support material (202), for example, the adhesive material (210) is attached to the flexible fabric (204).
  • a first stimuli-responsive porous material (212) is in contact with the therapeutic agent (208).
  • FIG. 3 shows article (300) with a support material (302)
  • the support material (302) comprises a flexible fabric (304), such as a flexible hydrophobic fabric, and a backing membrane (306).
  • the flexible fabric (304), such as a flexible hydrophobic fabric, and the backing membrane (306) are attached to each other.
  • matrix material loaded with a therapeutic agent (308) is in contact with the support material (302), for example, matrix material loaded with a therapeutic agent and/or a penetration enhancer (308) is in contact with the flexible fabric (304).
  • an adhesive material (310) is present and attached to the support material (302), for example, the adhesive material (310) is attached to the flexible fabric (304).
  • a first stimuli-responsive porous material (312) is in contact with the matrix material loaded with a therapeutic agent and/or a penetration enhancer (308).
  • FIG. 4 shows article (400) with a support material (402), the support material (402) comprises a flexible fabric (404), such as a flexible hydrophobic fabric, and a backing membrane (406).
  • the flexible fabric (404), such as a flexible hydrophobic fabric, and the backing membrane (406) are attached to each other.
  • matrix material loaded with a therapeutic agent (408) is in contact with the support material (402), for example, matrix material loaded with a therapeutic agent (408) is in contact with the flexible fabric (404).
  • an adhesive material (410) is present and attached to the support material (402), for example, the adhesive material (410) is attached to the flexible fabric (404).
  • a first stimuli- responsive porous material loaded with a therapeutic agent and/or a penetration enhancer (412) is in contact with the matrix material loaded with a therapeutic agent and/or a penetration enhancer (408).
  • FIG. 5 shows article (500) with a support material (502), the support material (502) comprises a flexible fabric (504), such as a flexible hydrophobic fabric, and a backing membrane (506).
  • the flexible fabric (504), such as a flexible hydrophobic fabric, and the backing membrane (506) are attached to each other.
  • an adhesive material (508) is present and attached to the support material (502), for example, the adhesive material (508) is attached to the flexible fabric (504).
  • a first stimuli-responsive porous material loaded with a therapeutic agent and/or a penetration enhancer (510) is in contact with the support material (502), for example, the adhesive material (508) is attached to the flexible fabric (504).
  • FIG. 6 shows a non-limiting exemplary aspect of the articles disclosed herein.
  • FIG. 6 shows a bandage (600), which comprises one or more articles disclosed herein, for example, article (602), which is inclusive of articles (100), (200), (300), (400), and (500) described above.
  • the one or more articles (602) can be arranges in a matrix (608).
  • the bandage (600) comprises an adhesive (606) on one side of the bandage.
  • the adhesive (606) and the article (602) are present on the same side of bandage (600).
  • the bandage is configured to covers a body part, such as, for example, finger (604).
  • FIG. 7 shows a non-limiting exemplary aspect of the articles disclosed herein.
  • FIG. 7 shows a joint sleeve (700), which comprises one or more articles disclosed herein, for example, article (702), which is inclusive of articles (100), (200), (300), (400), and (500) described above.
  • the one or more articles (702) are present on the inner surface of the joint sleeve (700).
  • the joint sleeve (700) comprises an elastomeric polymer (704), which can be made of a natural or synthetic polymer.
  • the first stimuli-responsive porous material can be a gel.
  • the first stimuli-responsive porous material can be a hydrogel.
  • the first stimuli-responsive porous material can be a polymer, such as a cross-linked polymer.
  • the first stimuli-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent. In another aspect, the first stimuli-responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 1% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 2% by weight of a therapeutic agent. In yet another aspect, the first stimuli- responsive porous material can be loaded with at least 3% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent.
  • the first stimuli-responsive porous material can be loaded with at least 5% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 6% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 7% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 8% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 9% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 15% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 20% by weight of a therapeutic agent.
  • the first stimuli-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, first stimuli-responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 3% by weight of a therapeutic agent and a penetration enhancer.
  • the first stimuli-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 6% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 8% by weight of a therapeutic agent and a penetration enhancer.
  • the first stimuli-responsive porous material can be loaded with at least 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 20% by weight of a therapeutic agent and a penetration enhancer.
  • the first stimuli-responsive porous material can be loaded with at least 0.1% by weight of a penetration enhancer. In yet another aspect, first stimuli-responsive porous material can be loaded with at least 0.5% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 1% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 2% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 3% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 4% by weight of a penetration enhancer.
  • the first stimuli-responsive porous material can be loaded with at least 5% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 6% by weight of a penetration enhancer. In yet another aspect, the first stimuli- responsive porous material can be loaded with at least 7% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 8% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 9% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 10% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 15% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with at least 20% by weight of a penetration enhancer.
  • the first stimuli-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent. In another aspect, the first stimuli-responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 1% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 3% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 4% by weight of a therapeutic agent.
  • the first stimuli-responsive porous material can be loaded with less than 5% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 6% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 7% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 8% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 9% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 10% by weight of a therapeutic agent. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 15% by weight of a therapeutic agent. In yet another aspect, the first stimuli- responsive porous material can be loaded with less than 20% by weight of a therapeutic agent.
  • the first stimuli-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, first stimuli-responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli- responsive porous material can be loaded with less than 1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 3% by weight of a therapeutic agent and a penetration enhancer.
  • the first stimuli-responsive porous material can be loaded with less than 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 6% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli- responsive porous material can be loaded with less than 8% by weight of a therapeutic agent and a penetration enhancer.
  • the first stimuli-responsive porous material can be loaded with less than 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 20% by weight of a therapeutic agent and a penetration enhancer.
  • the first stimuli-responsive porous material can be loaded with less than 0.1% by weight of a penetration enhancer. In yet another aspect, first stimuli- responsive porous material can be loaded with less than 0.5% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 1% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 2% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 3% by weight of a penetration enhancer. In yet another aspect, the first stimuli- responsive porous material can be loaded with less than 4% by weight of a penetration enhancer.
  • the first stimuli-responsive porous material can be loaded with less than 5% by weight of a penetration enhancer. In yet another aspect, the first stimuli- responsive porous material can be loaded with less than 6% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 7% by weight of a penetration enhancer. In yet another aspect, the first stimuli- responsive porous material can be loaded with less than 8% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 9% by weight of a penetration enhancer. In yet another aspect, the first stimuli- responsive porous material can be loaded with less than 10% by weight of a penetration enhancer. In yet another aspect, the first stimuli-responsive porous material can be loaded with less than 15% by weight of a penetration enhancer. In yet another aspect, the first stimuli- responsive porous material can be loaded with less than 20% by weight of a penetration enhancer.
  • the first stimuli-responsive porous material is not loaded with therapeutic agent or a penetration enhancer.
  • the first stimuli-responsive porous material can be a first thermo- responsive and/or mechanically -responsive porous material.
  • the first stimuli- responsive porous material can be a first thermo-responsive porous material.
  • the first stimuli-responsive porous material can be a first mechanically-responsive porous material.
  • the second stimuli-responsive porous material can be a gel.
  • the second stimuli-responsive porous material can be a hydrogel.
  • the second stimuli-responsive porous material can be a polymer, such as a cross-linked polymer.
  • the second stimuli-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent. In another aspect, the second stimuli-responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 1% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 2% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 3% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent.
  • the second stimuli- responsive porous material can be loaded with at least 5% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 6% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 7% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 8% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 9% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 15% by weight of a therapeutic agent. In yet another aspect, the second stimuli- responsive porous material can be loaded with at least 20% by weight of a therapeutic agent.
  • the second stimuli-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, second stimuli-responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli- responsive porous material can be loaded with at least 1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 3% by weight of a therapeutic agent and a penetration enhancer.
  • the second stimuli-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli- responsive porous material can be loaded with at least 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 6% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 8% by weight of a therapeutic agent and a penetration enhancer.
  • the second stimuli- responsive porous material can be loaded with at least 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 20% by weight of a therapeutic agent and a penetration enhancer.
  • the second stimuli-responsive porous material can be loaded with at least 0.1% by weight of a penetration enhancer. In yet another aspect, second stimuli- responsive porous material can be loaded with at least 0.5% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 1% by weight of a penetration enhancer. In yet another aspect, the second stimuli- responsive porous material can be loaded with at least 2% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 3% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 4% by weight of a penetration enhancer.
  • the second stimuli-responsive porous material can be loaded with at least 5% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 6% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 7% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 8% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 9% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 10% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 15% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with at least 20% by weight of a penetration enhancer.
  • the second stimuli-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent. In another aspect, the second stimuli-responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 1% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 3% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 4% by weight of a therapeutic agent.
  • the second stimuli-responsive porous material can be loaded with less than 5% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 6% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 7% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 8% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 9% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 10% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 15% by weight of a therapeutic agent. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 20% by weight of a therapeutic agent.
  • the second stimuli-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, second stimuli-responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli- responsive porous material can be loaded with less than 1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 3% by weight of a therapeutic agent and a penetration enhancer.
  • the second stimuli-responsive porous material can be loaded with less than 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 6% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 8% by weight of a therapeutic agent and a penetration enhancer.
  • the second stimuli-responsive porous material can be loaded with less than 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 20% by weight of a therapeutic agent and a penetration enhancer.
  • the second stimuli-responsive porous material can be loaded with less than 0.1% by weight of a penetration enhancer. In yet another aspect, second stimuli- responsive porous material can be loaded with less than 0.5% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 1% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 2% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 3% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 4% by weight of a penetration enhancer.
  • the second stimuli-responsive porous material can be loaded with less than 5% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 6% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 7% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 8% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 9% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 10% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 15% by weight of a penetration enhancer. In yet another aspect, the second stimuli-responsive porous material can be loaded with less than 20% by weight of a penetration enhancer.
  • the second stimuli-responsive porous material is not loaded with therapeutic agent or a penetration enhancer.
  • the second stimuli-responsive porous material can be a second thermo- responsive and/or mechanically-responsive porous material.
  • the second stimuli-responsive porous material can be a second thermo-responsive porous material.
  • the second stimuli-responsive porous material can be a second mechanically- responsive porous material.
  • the second stimuli-responsive porous material can be a first mechanically-responsive porous material.
  • the second stimuli-responsive porous material can be a first mechanically-responsive porous material.
  • the first stimuli-responsive porous material and the second stimuli- responsive porous material are loaded with different substances.
  • the first stimuli-responsive material is loaded with a therapeutic agent and the second stimuli-responsive material is loaded with a penetration enhancer.
  • the first stimuli-responsive material is not loaded and the second stimuli-responsive material is loaded with a penetration enhancer.
  • the first stimuli-responsive material is not loaded and the second stimuli-responsive material is loaded with a therapeutic agent.
  • the first thermo-responsive porous material can be a gel. In another aspect, the first thermo-responsive porous material can be a hydrogel. In yet another aspect, the first thermo-responsive porous material can be a polymer, such as a cross-linked polymer. In one aspect, the first thermo-responsive porous material can have a LCST close to the body temperature of a human, for example, the first thermo-responsive porous material can have a LCST from 27 °C to 40 °C, from 32 °C to 40 °C, from 32 °C to 38 °C, or from 32 °C to 46 °C.
  • the first thermo-responsive porous material can comprise poly( - isopropylacrylamide), poly(N-vinylcaprolactam), or poly(vinyl methyl ether), co-polymers thereof, or a mixture thereof.
  • the first thermo-responsive porous material can comprise poly(N-isopropylacrylamide).
  • the first thermo-responsive porous material can comprise poly(N-vinylcaprolactam).
  • the first thermo-responsive porous material can comprise poly(vinyl methyl ether).
  • the first thermo-responsive porous material is poly(N-isopropylacrylamide).
  • the first thermo-responsive porous material is poly(N-vinylcaprolactam).
  • the first thermo-responsive porous material is poly(vinyl methyl ether). In yet another aspect, the first thermo-responsive porous material can comprise a copolymer comprising poly(N-isopropylacrylamide). In yet another aspect, the first thermo-responsive porous material can comprise a copolymer comprising poly( -vinylcaprolactam). In yet another aspect, the first thermo-responsive porous material can comprise a copolymer comprising poly(vinyl methyl ether). In yet another aspect, the first thermo-responsive porous material is a copolymer comprising poly( -isopropylacrylamide).
  • the first thermo- responsive porous material is a copolymer comprising poly(N-vinylcaprolactam). In yet another aspect, the first thermo-responsive porous material is a copolymer comprising poly(vinyl methyl ether).
  • the first thermo-responsive porous material comprises a thermo- responsive polymer with a number average molecular weight from 20 kDa to 50 kDa. In another aspect, the first thermo-responsive porous material comprises a thermo-responsive polymer with a number average molecular weight from 50 kDa to 100 kDa. In yet another aspect, the first thermo-responsive porous material comprises a thermo-responsive polymer with a number average molecular weight from 100 kDa to 200 kDa. In yet another aspect, the first thermo-responsive porous material comprises a thermo-responsive polymer with a number average molecular weight from 200 kDa to 500 kDa.
  • the first thermo-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent. In yet another aspect, first thermo-responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 1% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 2% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 3% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent.
  • the first thermo-responsive porous material can be loaded with at least 5% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 6% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 7% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 8% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 9% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 15% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 20% by weight of a therapeutic agent.
  • the first thermo-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, first thermo-responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 3% by weight of a therapeutic agent and a penetration enhancer.
  • the first thermo-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 6% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 8% by weight of a therapeutic agent and a penetration enhancer.
  • the first thermo-responsive porous material can be loaded with at least 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 20% by weight of a therapeutic agent and a penetration enhancer.
  • the first thermo-responsive porous material can be loaded with at least 0.1% by weight of a penetration enhancer. In yet another aspect, first thermo-responsive porous material can be loaded with at least 0.5% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 1% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 2% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 3% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 4% by weight of a penetration enhancer.
  • the first thermo-responsive porous material can be loaded with at least 5% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 6% by weight of a penetration enhancer. In yet another aspect, the first thermo- responsive porous material can be loaded with at least 7% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 8% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 9% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 10% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 15% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with at least 20% by weight of a penetration enhancer.
  • the first thermo-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent. In yet another aspect, first thermo-responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 1% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 3% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 4% by weight of a therapeutic agent.
  • the first thermo- responsive porous material can be loaded with less than 5% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 6% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 7% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 8% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 9% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 10% by weight of a therapeutic agent. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 15% by weight of a therapeutic agent. In yet another aspect, the first thermo- responsive porous material can be loaded with less than 20% by weight of a therapeutic agent.
  • the first thermo-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, first thermo-responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo- responsive porous material can be loaded with less than 1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 3% by weight of a therapeutic agent and a penetration enhancer.
  • the first thermo-responsive porous material can be loaded with less than 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 6% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo- responsive porous material can be loaded with less than 8% by weight of a therapeutic agent and a penetration enhancer.
  • the first thermo-responsive porous material can be loaded with less than 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 20% by weight of a therapeutic agent and a penetration enhancer.
  • the first thermo-responsive porous material can be loaded with less than 0.1% by weight of a penetration enhancer. In yet another aspect, first thermo- responsive porous material can be loaded with less than 0.5% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 1% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 2% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 3% by weight of a penetration enhancer. In yet another aspect, the first thermo- responsive porous material can be loaded with less than 4% by weight of a penetration enhancer.
  • the first thermo-responsive porous material can be loaded with less than 5% by weight of a penetration enhancer. In yet another aspect, the first thermo- responsive porous material can be loaded with less than 6% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 7% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 8% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 9% by weight of a penetration enhancer. In yet another aspect, the first thermo- responsive porous material can be loaded with less than 10% by weight of a penetration enhancer. In yet another aspect, the first thermo-responsive porous material can be loaded with less than 15% by weight of a penetration enhancer. In yet another aspect, the first thermo- responsive porous material can be loaded with less than 20% by weight of a penetration enhancer.
  • the first thermo-responsive porous material is not loaded with therapeutic agent or a penetration enhancer.
  • Poly( -isopropylacrylamide) is known in the art as is described by Vihola, H., et al (J. Biomaterials 2005, 26, 3055); Li, J., et al, (Int. J. Pharmacol. 2006, 2, 513); Zhu, Z., et al. A. (ACS Nano 2009, 3, 3595); Nash, M. A., et al. (Nano Lett. 2009, 10, 85); Zhang, X, et al, (Nano Lett. 2011, 1 1, 3239); and Wu, T., et al. (S. Chem. Mater. 2011, 23, 2370).
  • Poly(N-vinylcaprolactam) is known in the art as is described by Medeiros, S. F. et al, (J. Polym. Sci. A: Polym. Chem. 2010, 48, 3932); Imaz, A., et al. (Polym. Sci. A: Polym. Chem. 2010, 48, 1173); Cakal, E. I., et al. (Ind. Eng. Chem. Res. 2010, 49, 1 1741); Srivastava, A., et al. (J. Mater. Sci.: Materials in Medicine 2010, 21, 2937); and Balaceanu, A., et al.
  • Poly(vinyl methyl ether) is known in the art and is described by Kabra, B.G., et al. (Polymer, 1992, 33, 990); Pich, A., et al. (Polymer 2002, 43, 5723); and Kharlampieva, E., et al. (Macromolecules 2005, 38, 10523).
  • the second thermo-responsive porous material can be a gel. In another aspect, the second thermo-responsive porous material can be a hydrogel. In yet another aspect, the second thermo-responsive porous material can be a polymer, such as a cross-linked polymer. In one aspect, the second thermo-responsive porous material can comprise poly(N- isopropylacrylamide), poly(N-vinylcaprolactam), or poly(vinyl methyl ether), a co-polymer thereof, or a mixture thereof. In another aspect, the second thermo-responsive porous material can comprise poly(N-isopropylacrylamide). In yet another aspect, the second thermo- responsive porous material can comprise poly(N-vinylcaprolactam).
  • the second thermo-responsive porous material can comprise poly(vinyl methyl ether). In another aspect, the second thermo-responsive porous material is poly(N-isopropylacrylamide). In yet another aspect, the second thermo-responsive porous material is poly(N-vinylcaprolactam). In yet another aspect, the second thermo-responsive porous material is poly(vinyl methyl ether). In yet another aspect, the second thermo-responsive porous material can comprise a copolymer comprising poly(N-isopropylacrylamide). In yet another aspect, the second thermo-responsive porous material can comprise a copolymer comprising poly(N-vinylcaprolactam).
  • the second thermo-responsive porous material can comprise a copolymer comprising poly(vinyl methyl ether). In yet another aspect, the second thermo-responsive porous material is a copolymer comprising poly(N-isopropylacrylamide). In yet another aspect, the second thermo-responsive porous material is a copolymer comprising poly( - vinylcaprolactam). In yet another aspect, the second thermo-responsive porous material is a copolymer comprising poly(vinyl methyl ether).
  • the second thermo-responsive porous material comprises a thermo-responsive polymer with a number average molecular weight from 20 kDa to 50 kDa. In another aspect, the second thermo-responsive porous material comprises a thermo-responsive polymer with a number average molecular weight from 50 kDa to 100 kDa. In yet another aspect, the second thermo-responsive porous material comprises a thermo-responsive polymer with a number average molecular weight from 100 kDa to 200 kDa. In yet another aspect, the second thermo-responsive porous material comprises a thermo-responsive polymer with a number average molecular weight from 200 kDa to 500 kDa.
  • the second thermo-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent. In yet another aspect, second thermo-responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 1% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 2% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 3% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent.
  • the second thermo-responsive porous material can be loaded with at least 5% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 6% by weight of a therapeutic agent. In yet another aspect, the second thermo- responsive porous material can be loaded with at least 7% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 8% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 9% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 15% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 20% by weight of a therapeutic agent.
  • the second thermo-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, second thermo-responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 3% by weight of a therapeutic agent and a penetration enhancer.
  • the second thermo-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo- responsive porous material can be loaded with at least 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 6% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 8% by weight of a therapeutic agent and a penetration enhancer.
  • the second thermo- responsive porous material can be loaded with at least 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 20% by weight of a therapeutic agent and a penetration enhancer.
  • the second thermo-responsive porous material can be loaded with at least 0.1% by weight of a penetration enhancer. In yet another aspect, second thermo-responsive porous material can be loaded with at least 0.5% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 1% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 2% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 3% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 4% by weight of a penetration enhancer.
  • the second thermo-responsive porous material can be loaded with at least 5% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 6% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 7% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 8% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 9% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 10% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 15% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with at least 20% by weight of a penetration enhancer.
  • the second thermo-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent. In yet another aspect, second thermo- responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 1% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 3% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 4% by weight of a therapeutic agent.
  • the second thermo-responsive porous material can be loaded with less than 5% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 6% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 7% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 8% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 9% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 10% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 15% by weight of a therapeutic agent. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 20% by weight of a therapeutic agent.
  • the second thermo-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, second thermo-responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 3% by weight of a therapeutic agent and a penetration enhancer.
  • the second thermo-responsive porous material can be loaded with less than 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 6% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 8% by weight of a therapeutic agent and a penetration enhancer.
  • the second thermo-responsive porous material can be loaded with less than 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 20% by weight of a therapeutic agent and a penetration enhancer.
  • the second thermo-responsive porous material can be loaded with less than 0.1% by weight of a penetration enhancer. In yet another aspect, second thermo-responsive porous material can be loaded with less than 0.5% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 1% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 2% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 3% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 4% by weight of a penetration enhancer.
  • the second thermo-responsive porous material can be loaded with less than 5% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 6% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 7% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 8% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 9% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 10% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 15% by weight of a penetration enhancer. In yet another aspect, the second thermo-responsive porous material can be loaded with less than 20% by weight of a penetration enhancer.
  • the second thermo-responsive porous material is not loaded with therapeutic agent or a penetration enhancer.
  • the first thermo-responsive porous material and the second thermo-responsive porous material are loaded with different substances.
  • the first thermo-responsive material is loaded with a therapeutic agent and the second thermo- responsive material is loaded with a penetration enhancer.
  • the first thermo- responsive material is not loaded and the second thermo-responsive material is loaded with a penetration enhancer.
  • the first thermo-responsive material is not loaded and the second thermo-responsive material is loaded with a therapeutic agent.
  • the first mechanically-responsive porous material can be a gel.
  • the first mechanically -responsive porous material can be a hydrogel.
  • the first mechanically -responsive porous material can be a polymer, such as a cross-linked polymer.
  • the first mechanically -responsive porous material can comprise gellan gum.
  • the first mechanically-responsive porous material can comprise gellan gum and a cross-linked polymer selected from polylactic acid, poly(lactic-co-glycolic acid), polyethylene glycol, polycaprolactam, polyesters, polyesteramides, polyanhydrides, polycarbonates, poly(amino acids), polyacetyls, polycyanoacrylates, blends and copolymers thereof.
  • the cross-linked polymer is selected from polylactic acid, poly(lactic- co-glycolic acid), blends and copolymers thereof.
  • the polymer can have a number average molecular weight from 20 kDa to 50 kDa. In another aspect, the polymer can have a number average molecular weight from 50 kDa to 100 kDa. In yet another aspect, the polymer can have a number average molecular weight from 100 kDa to 200 kDa. In yet another aspect, the polymer can have a number average molecular weight from 200 kDa to 500 kDa.
  • the first mechanically-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent. In yet another aspect, first mechanically- responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 1% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 2% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 3% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent.
  • the first mechanically-responsive porous material can be loaded with at least 5% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 6% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 7% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 8% by weight of a therapeutic agent. In yet another aspect, the first mechanically -responsive porous material can be loaded with at least 9% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent. In yet another aspect, the first mechanically -responsive porous material can be loaded with at least 15% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 20% by weight of a therapeutic agent.
  • the first mechanically-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, first mechanically-responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with at least 1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 3% by weight of a therapeutic agent and a penetration enhancer.
  • the first mechanically-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with at least 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically- responsive porous material can be loaded with at least 6% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with at least 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 8% by weight of a therapeutic agent and a penetration enhancer.
  • the first mechanically -responsive porous material can be loaded with at least 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 20% by weight of a therapeutic agent and a penetration enhancer.
  • the first mechanically-responsive porous material can be loaded with at least 0.1% by weight of a penetration enhancer. In yet another aspect, first mechanically -responsive porous material can be loaded with at least 0.5% by weight of a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with at least 1% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 2% by weight of a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with at least 3% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 4% by weight of a penetration enhancer.
  • the first mechanically -responsive porous material can be loaded with at least 5% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 6% by weight of a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with at least 7% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 8% by weight of a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with at least 9% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 10% by weight of a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with at least 15% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with at least 20% by weight of a penetration enhancer.
  • the first mechanically-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent. In yet another aspect, first mechanically- responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 1% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 3% by weight of a therapeutic agent. In yet another aspect, the first mechanically- responsive porous material can be loaded with less than 4% by weight of a therapeutic agent.
  • the first mechanically-responsive porous material can be loaded with less than 5% by weight of a therapeutic agent. In yet another aspect, the first mechanically- responsive porous material can be loaded with less than 6% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 7% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 8% by weight of a therapeutic agent. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 9% by weight of a therapeutic agent. In yet another aspect, the first mechanically- responsive porous material can be loaded with less than 10% by weight of a therapeutic agent.
  • the first mechanically-responsive porous material can be loaded with less than 15% by weight of a therapeutic agent. In yet another aspect, the first mechanically- responsive porous material can be loaded with less than 20% by weight of a therapeutic agent. [00119] In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, first mechanically-responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 1% by weight of a therapeutic agent and a penetration enhancer.
  • the first mechanically-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 3% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 6% by weight of a therapeutic agent and a penetration enhancer.
  • the first mechanically-responsive porous material can be loaded with less than 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 8% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the first mechanically- responsive porous material can be loaded with less than 20% by weight of a therapeutic agent and a penetration enhancer.
  • the first mechanically-responsive porous material can be loaded with less than 0.1% by weight of a penetration enhancer. In yet another aspect, first mechanically-responsive porous material can be loaded with less than 0.5% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 1% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 2% by weight of a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with less than 3% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 4% by weight of a penetration enhancer.
  • the first mechanically -responsive porous material can be loaded with less than 5% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 6% by weight of a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with less than 7% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 8% by weight of a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with less than 9% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 10% by weight of a penetration enhancer. In yet another aspect, the first mechanically -responsive porous material can be loaded with less than 15% by weight of a penetration enhancer. In yet another aspect, the first mechanically-responsive porous material can be loaded with less than 20% by weight of a penetration enhancer.
  • the first mechanically-responsive porous material is not loaded with therapeutic agent or a penetration enhancer.
  • the first mechanically-responsive porous material and the second mechanically-responsive porous material are loaded with different substances.
  • the first mechanically-responsive material is loaded with a therapeutic agent and the second mechanically-responsive material is loaded with a penetration enhancer.
  • the first mechanically-responsive material is not loaded and the second mechanically- responsive material is loaded with a penetration enhancer.
  • the first mechanically-responsive material is not loaded and the second mechanically-responsive material is loaded with a therapeutic agent.
  • the second mechanically-responsive porous material can be a gel.
  • the second mechanically-responsive porous material can be a hydrogel.
  • the second mechanically-responsive porous material can be a polymer, such as a cross-linked polymer.
  • the second mechanically-responsive porous material can comprise gellan gum.
  • the second mechanically-responsive porous material can comprise gellan gum and a cross-linked polymer selected from polylactic acid, poly(lactic- co-glycolic acid), polyethylene glycol, polycaprolactam, polyesters, polyesteramides, polyanhydrides, polycarbonates, poly(amino acids), polyacetyls, polycyanoacrylates, blends and copolymers thereof.
  • the cross-linked polymer is selected from polylactic acid, poly(lactic -co-glycolic acid), blends and copolymers thereof.
  • the polymer can have a number average molecular weight from 20 kDa to 50 kDa. In another aspect, the polymer can have a number average molecular weight from 50 kDa to 100 kDa. In yet another aspect, the polymer can have a number average molecular weight from 100 kDa to 200 kDa. In yet another aspect, the polymer can have a number average molecular weight from 200 kDa to 500 kDa.
  • the second mechanically-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent. In yet another aspect, second mechanically -responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 1% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 2% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 3% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent.
  • the second mechanically-responsive porous material can be loaded with at least 5% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 6% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 7% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 8% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 9% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 15% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 20% by weight of a therapeutic agent.
  • the second mechanically-responsive porous material can be loaded with at least 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, second mechanically-responsive porous material can be loaded with at least 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically- responsive porous material can be loaded with at least 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 3% by weight of a therapeutic agent and a penetration enhancer.
  • the second mechanically-responsive porous material can be loaded with at least 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 6% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically- responsive porous material can be loaded with at least 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically -responsive porous material can be loaded with at least 8% by weight of a therapeutic agent and a penetration enhancer.
  • the second mechanically-responsive porous material can be loaded with at least 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically- responsive porous material can be loaded with at least 20% by weight of a therapeutic agent and a penetration enhancer.
  • the second mechanically-responsive porous material can be loaded with at least 0.1% by weight of a penetration enhancer. In yet another aspect, second mechanically -responsive porous material can be loaded with at least 0.5% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 1% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 2% by weight of a penetration enhancer. In yet another aspect, the second mechanically -responsive porous material can be loaded with at least 3% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 4% by weight of a penetration enhancer.
  • the second mechanically-responsive porous material can be loaded with at least 5% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 6% by weight of a penetration enhancer. In yet another aspect, the second
  • the mechanically -responsive porous material can be loaded with at least 7% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 8% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 9% by weight of a penetration enhancer. In yet another aspect, the second mechanically -responsive porous material can be loaded with at least 10% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with at least 15% by weight of a penetration enhancer. In yet another aspect, the second mechanically- responsive porous material can be loaded with at least 20% by weight of a penetration enhancer.
  • the second mechanically-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent. In yet another aspect, second mechanically-responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 1% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 3% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 4% by weight of a therapeutic agent.
  • the second mechanically -responsive porous material can be loaded with less than 5% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 6% by weight of a therapeutic agent. In yet another aspect, the second mechanically -responsive porous material can be loaded with less than 7% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 8% by weight of a therapeutic agent. In yet another aspect, the second mechanically -responsive porous material can be loaded with less than 9% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 10% by weight of a therapeutic agent. In yet another aspect, the second mechanically -responsive porous material can be loaded with less than 15% by weight of a therapeutic agent. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 20% by weight of a therapeutic agent.
  • the second mechanically-responsive porous material can be loaded with less than 0.1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, second mechanically-responsive porous material can be loaded with less than 0.5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 1% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 2% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically- responsive porous material can be loaded with less than 3% by weight of a therapeutic agent and a penetration enhancer.
  • the second mechanically-responsive porous material can be loaded with less than 4% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 5% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 6% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 7% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically- responsive porous material can be loaded with less than 8% by weight of a therapeutic agent and a penetration enhancer.
  • the second mechanically-responsive porous material can be loaded with less than 9% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 10% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 15% by weight of a therapeutic agent and a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 20% by weight of a therapeutic agent and a penetration enhancer.
  • the second mechanically-responsive porous material can be loaded with less than 0.1% by weight of a penetration enhancer. In yet another aspect, second mechanically-responsive porous material can be loaded with less than 0.5% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 1% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 2% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 3% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 4% by weight of a penetration enhancer.
  • the second mechanically-responsive porous material can be loaded with less than 5% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 6% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 7% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 8% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 9% by weight of a penetration enhancer. In yet another aspect, the second mechanically -responsive porous material can be loaded with less than 10% by weight of a penetration enhancer. In yet another aspect, the second mechanically-responsive porous material can be loaded with less than 15% by weight of a penetration enhancer. In yet another aspect, the second mechanically- responsive porous material can be loaded with less than 20% by weight of a penetration enhancer.
  • the second mechanically-responsive porous material is not loaded with therapeutic agent or a penetration enhancer.
  • the therapeutic agent is a pharmaceutical agent.
  • the therapeutic agent can be in the form of a gel, a paste, a foam, a powder, agglomerated particles, a microencapsulated liquid, a suspension, a liquid, and combinations thereof.
  • the therapeutic agent can be in the form of a microencapsulated liquid, a suspension or a liquid, or a mixture thereof.
  • the therapeutic agent comprises a non-steroidal antiinflammatory drug (NSAID), a steroid drug, an antibiotic, an anesthetic agent, nicotine, fentanyl, estrogen, testosterone, estradiol, clonidine, nitroglycerine, an antimicrobial agent, an antifungal agent, a cosmetic agent, a motion sickness agent, or an anti-hypertensive agent, or a mixture thereof, and pharmaceutically acceptable salts and esters thereof.
  • NSAID non-steroidal antiinflammatory drug
  • the therapeutic agent comprises anti-inflammatory drugs, both steroidal (e.g., hydrocortisone, prednisolone, triamcinolone) and nonsteroidal (e.g., naproxen, piroxicam); antibacterials (e.g., penicillins such as penicillin V, cephalosporins such as cephalexin, erythromycin, tetracycline, gentamycin, sulfathiazole, nitrofurantoin, and quinolones such as norfloxacin, flumequine, and ibafloxacin); antiprotozoals (e.g., metronidazole); antifungals (e.g., nystatin); coronary vasodilators (e.g., nitroglycerin); calcium channel blockers (e.g., nifedipine, diltiazem);
  • antibacterials e.g., penicillins such as penicillin V, cephalosporin
  • bronchodilators e.g., theophylline, pirbuterol, salmeterol, isoproterenol
  • enzyme inhibitors such as collagenase inhibitors, protease inhibitors, elastase inhibitors, lipoxygenase inhibitors (e.g., zileuton), and angiotensin converting enzyme inhibitors (e.g., captopril, lisinopril); other antihypertensives (e.g., propranolol); leukotriene antagonists; anti-ulceratives such as H2 antagonists; steroidal hormones (e.g., progesterone, testosterone, estradiol); antivirals and/or immunomodulators (e.g., l-isobutyl-lH-imidazo[4,5-c]quinolin-4-amine, l-(2-hydroxy-2- methylpropyl)-lH-imidazo[4,5-c]quinoline-4-amine, and
  • Pat. No. 4,689,338, acyclovir local anesthetics (e.g., benzocaine, propofol); cardiotonics (e.g., digitalis, digoxin); antitussives (e.g., codeine, dextromethorphan); antihistamines (e.g., diphenhydramine, chlorpheniramine, terfenadine); narcotic analgesics (e.g., morphine, fentanyl); peptide hormones (e.g., human or animal growth hormones, LHRH); sex hormones (e.g., estrogens, testosterone, progestins such as levonorgestrel, norethindrone, gestodene); cardioactive products such as atriopeptides; proteinaceous products (e.g., insulin); enzymes (e.g., anti-plaque enzymes, lysozyme, dextranase); antinauseants
  • anticonvulsants e.g., carbamazine
  • immunosuppressives e.g., cyclosporine
  • psychotherapeutics e.g., diazepam
  • sedatives e.g., phenobarbital
  • anticoagulants e.g., heparin
  • analgesics e.g., acetaminophen
  • antimigraine agents e.g., ergotamine, melatonin, sumatriptan
  • antiarrhythmic agents e.g., flecainide
  • antiemetics e.g., metaclopromide, ondansetron
  • anticancer agents e.g., methotrexate, 5-fluouracil
  • neurologic agents such as anxiolytic drugs; hemostatics; anti-obesity agents; and the like, and a mixture thereof, and pharmaceutically acceptable salts and esters thereof.
  • the therapeutic agent comprises an NSAID.
  • Suitable NSAIDs include, but are not limited to, acetylsalicylic acid, celecoxib, dexdetoprofen, diclofenac, diflunisal, etodolac, etoricoxib, fenoprofen, firocoxib, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, licofelone, licofelone, lornoxicam, loxoprofen, lumiracoxib,
  • the therapeutic agent comprises a protein, peptide, antibody, or oligo nucleic acid.
  • the therapeutic agent can comprise reicade, humirainsulin, growth hormone, or epoetinalfa, or a combination thereof. The transdermal delivery of such therapeutic agents is described in Chen Y, et al. Nat Biotechnol.
  • the article comprises one or more penetration enhancers.
  • the article can also further comprise other useful pharmaceutical excipients such as a softening agent (softeners), a solubilizer.
  • Suitable materials include, but are not limited to, Cs -C36 fatty acids such as isostearic acid, octanoic acid, and oleic acid; C8-C36 fatty alcohols such as oleyl alcohol and lauryl alcohol; lower alkyl esters of C 8 -C36 fatty acids such as ethyl oleate, isopropyl myristate, butyl stearate, and methyl laurate; di(lower) alkyl esters of Ce -Cs diacids such as diisopropyladipate; monoglycerides of C 8 -C36 fatty acids such as glycerylmonolaurate; tetraglycol (tetrahydrofurfuryl alcohol polyethylene glycol ether); tetraethylene glyco
  • Alkylaryl ethers of polyethylene oxide, polyethylene oxide monomethyl ethers, and polyethylene oxide dimethyl ethers are also suitable, as are solubilizers such as glycerol and N-methyl pyrrolidone.
  • Terpenes are another useful class of additives, including pinene, d-limonene, carene, terpineol, terpinen-4-ol, carveol, carvone, pulegone, piperitone, menthone, menthol, neomenthol, thymol, camphor, bomeol, citral, ionone, and cineole, alone or in any combination.
  • the article comprises glycerylmonolaurate, terpineol, lauryl alcohol, tetraglycol, tetraethylene glycol, propylene glycol, isopropyl myristate, dimethyl sulfoxide (DMSO), isopropyl alcohol, polysorbate, ethyl oleate, methyl laurate, or 2-(2-ethoxyethoxy)ethanol, or a mixture thereof.
  • DMSO dimethyl sulfoxide
  • the article can comprise two or more formulations comprising the same therapeutic agent but with different penetration enhancers.
  • Such article can, thus, comprise a fast acting formulation and a sustained release formulation.
  • the different formulations can be present at different location or in different materials in the article.
  • a fast acting formulation can be present in a first stimuli-responsive porous material and sustained release formulation can be present in a second stimuli-responsive porous material and/or in the matrix material.
  • An article comprising both a fast acting formulation and a sustained release formulation can provide both fast and sustained of the therapeutic agent, thereby, providing immediate and long-term relief for a subject using the article.
  • Suitable adhesives include, but are not limited to, acrylics, natural and synthetic rubbers, ethylene vinyl acetate, poly(alpha-olefins), vinyl ethers, and silicones.
  • the adhesive can be in the form of copolymers, bicontinuous adhesives, hydrogels, latex emulsions, macromers, and block copolymers.
  • Suitable block copolymers are commercially available from Shell Oil Company (Houston, Tex.) under the trade designation KRATON.
  • the adhesive include, but are not limited to, acrylics, poly(olefins),
  • Acrylic adhesives are disclosed, for example, in U.S. Pat. Nos. 3,239,478, 3,935,338, 5,169,727, RE 24,906, 4,952,650, 4, 181,752, 5,986,01 1, 5,637,646 and 5,753,768.
  • a suitable class of acrylate adhesives is the reaction product of at least one alkyl acrylate with at least one reinforcing co-monomer.
  • Suitable alkyl acrylates are those having a homopolymer glass transition temperature below about -10 °C and include, for example, n-butyl acrylate, 2-ethylhexylacrylate, isoctylacrylate, isononyl acrylate, ethylene monoacrylate, octadecyl acrylate and the like.
  • Suitable reinforcing monomers include, for example, acrylic acid, itaconic acid, isobornyl acrylate, N, N-dimethylacrylamide, N-vinyl caprolactam, N-vinyl pyrrolidone, and the like.
  • the adhesives can be prepared and coated using a variety of standard methods.
  • the adhesives can be polymers that are dispersed in solvent or water and coated onto the support material. If a solvent borne or water borne adhesive composition is employed, then the adhesive can undergo a drying step to remove all or a majority of the carrier liquid.
  • the adhesive can be cured using an energy source (e.g., heat, UV radiation, e-beam, and the like).
  • adhesives can be applied without dispersal in a solvent or water using a variety of methods, such as, for example, melting or extruding the adhesive onto a liner or molding tool.
  • the adhesive can be cross-linked with an energy source such as heat, UV radiation, e-beam radiation, and the like.
  • monomeric pre-adhesive compositions can be coated onto a liner or molding tool and polymerized and cross-linked with an energy source, as described above. f. Support material
  • the support material is flexible. In another aspect, the support material is elastic. In yet another aspect, the support material is hydrophobic. In yet another aspect, the outer surface of the support material is hydrophobic. In yet another aspect, the inner surface of the support material is hydrophobic. In yet another aspect, the inner and outer surfaces of the support material are hydrophobic. In yet another aspect, the support material comprises kratonspunbondstyrenic block copolymers fabrics.
  • the support material comprises a backing layer.
  • the support material comprises a fabric layer.
  • the fabric layer can be a flexible fabric layer.
  • the fabric layer can be an elastic fabric layer.
  • the fabric layer can be a flexible hydrophobic fabric layer.
  • the support material is continuous, for example, in the shape of a tube.
  • the adhesive is present on a portion of the support material.
  • the first stimuli-responsive material is present on a portion of the support material.
  • the matrix material is present on a portion of the support material. g. Matrix material
  • the matrix material is a porous matrix material.
  • the matrix material is a polymer, such as a cross-linked polymer.
  • the polymer is selected from polylactic acid, poly(lactic-co-glycolic acid), polyethylene glycol,
  • the cross-linked polymer is selected from polylactic acid, poly(lactic-co-glycolic acid), blends and copolymers thereof.
  • the cross-linked polymer is polylactic acid.
  • the polymer can have a number average molecular weight from 3 kDa to 1,000 kDa. In another aspect, the polymer can have a number average molecular weight from 3 kDa to 500 kDa. In yet another aspect, the polymer can have a number average molecular weight from 3 kDa to 300 kDa. In yet another aspect, the polymer can have a number average molecular weight from 3 kDa to 200 kDa. In yet another aspect, the polymer can have a number average molecular weight from 3 kDa to 100 kDa. In yet another aspect, the polymer can have a number average molecular weight from 3 kDa to 80 kDa.
  • the polymer can have a number average molecular weight from 3 kDa to 60 kDa. In yet another aspect, the polymer can have a number average molecular weight from 3 kDa to 40 kDa. In yet another aspect, the polymer can have a number average molecular weight from 3 kDa to 20 kDa. In yet another aspect, the polymer can have a number average molecular weight from 20 kDa to 80 kDa. In yet another aspect, the polymer can have a number average molecular weight from 20 kDa to 60 kDa.
  • Also disclosed herein is a method of treating a disorder comprising application of an article disclosed herein to a subject in need of treatment of the disorder.
  • the therapeutic agent is released from article upon the application of the article.
  • the therapeutic agent and the penetration enhancer are released from article upon the application of the article.
  • a therapeutically effective amount of the therapeutic agent is released upon the application of the article.
  • a therapeutically effective amount of the therapeutic agent is transdermally administered to the subject upon the application of the article.
  • the treatment of a disorder comprises reducing pain of the subject.
  • the disorder is osteoarthritis, rheumatoid arthritis, post-surgical pain, trauma, a burn, a sting, a diabetic leg ulcer, scleroderma, or an infection.
  • the application of the article treats a wound.
  • the article is applied over a desired part of the body.
  • the first and/or second stimuli-responsive material is applied over a desired part of the body.
  • the article is applied at the location of a joint of the subject.
  • the joint is a DIP.
  • the joint is the basilar joint of the thumb (trapezium) and/or the first three bones of the thumb (metacarpal).
  • the joint is a finger joint, a toe joint, knee, elbow, shoulder, wrist, or ankle.
  • the joint is the metatarsophalangeal joint.
  • the article is applied over a wound.
  • the article is applied over an inflamed portion of the body.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Cette invention concerne des articles et des procédés liés à un article comprenant a) un premier matériau poreux réagissant à des stimuli, le premier matériau poreux réagissant aux stimuli ayant un premier et un second côtés opposés l'un à l'autre ; b) un agent thérapeutique ; et c) un matériau de support. Les articles et les procédés sont utiles pour l'administration transdermique d'agents thérapeutiques.
PCT/US2014/032662 2013-04-03 2014-04-02 Articles et procédés liés à l'administration transdermique d'un agent thérapeutique Ceased WO2014165582A1 (fr)

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US61/807,803 2013-04-03

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040258727A1 (en) * 2003-05-28 2004-12-23 Lina Liu Ophthalmic biomaterials and preparation thereof
US20080220149A1 (en) * 2002-12-23 2008-09-11 Howard Allen Ketelson Compositions and methods for inhibiting protein on surfaces
US20090263441A1 (en) * 2008-04-18 2009-10-22 Warsaw Orthopedic, Inc. Drug depots having diffreent release profiles for reducing, preventing or treating pain and inflammation
US20110027340A1 (en) * 2009-07-31 2011-02-03 Warsaw Orthopedic, Inc. Implantable drug depot for weight control

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080220149A1 (en) * 2002-12-23 2008-09-11 Howard Allen Ketelson Compositions and methods for inhibiting protein on surfaces
US20040258727A1 (en) * 2003-05-28 2004-12-23 Lina Liu Ophthalmic biomaterials and preparation thereof
US20090263441A1 (en) * 2008-04-18 2009-10-22 Warsaw Orthopedic, Inc. Drug depots having diffreent release profiles for reducing, preventing or treating pain and inflammation
US20110027340A1 (en) * 2009-07-31 2011-02-03 Warsaw Orthopedic, Inc. Implantable drug depot for weight control

Non-Patent Citations (1)

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Title
POPESCU ET AL.: "pH-Responsive Hydrogel/Liposome Soft Nanocomposites For Tuning Drug Release", BIOMACROMOLECULES, vol. 12, 5 July 2011 (2011-07-05), pages 3023 - 3030 *

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