CN1760227A - Nano granules possessing hydrophobic core and hydrophilic surface, preparation method and application - Google Patents

Abstract

The invention belongs to the technical field of amphiphilic nanometer materials, in particular to a nanoparticle with a hydrophobic core and a hydrophilic surface, a preparation method and application thereof. The nanoparticles of the present invention contain a hydrophobic polymer block of polyalkyl acrylate or polyalkyl methacrylate and a hydrophilic unsaturated monomer or a polymer modified by the hydrophilic unsaturated monomer. Hydrophilic polymer block of chitosan. It is prepared according to the following steps: under the action of an initiator, the amino group of chitosan is radicalized, and combined with a hydrophilic unsaturated monomer and an alkyl acrylate or an alkyl methacrylate to obtain an amphoteric tri-block copolymer . It can be used in the production of medicines, nutrition and cosmetics. Compared with the prior art, it has the characteristics of good stability and high loading of active ingredients.

Description

Nanoparticles with hydrophobic core and hydrophilic surface, preparation method and application thereof

technical field

The invention belongs to the technical field of amphiphilic nanometer materials, and specifically relates to a block copolymer nanoparticle with a hydrophobic core and a hydrophilic surface, a preparation method and application thereof.

Background technique

Modern nanotechnology and nanoscience refer to the science of studying the physical and chemical properties and functions of substances with a particle size of 1-100nm. It can assemble and create substances with specific functions by directly manipulating individual atoms and molecules. Nanoparticles are made of high molecular substances, and active ingredients can be dissolved, adsorbed or encapsulated in the material. Generally, nanoparticles have the functions of slow release, targeting and protection of active ingredients, which can improve efficacy and reduce side effects. Nanoparticles are not easy to block blood vessels, and can pass through the endothelial wall to reach the target site from intracellular or intercellular, and can also pass through human capillaries or even the blood-brain barrier (BBB) to play a role. Nanoparticles have a high degree of dispersion and a huge surface area. When the size is reduced by 3 orders of magnitude, the surface area is increased by 6 orders of magnitude. It has a higher load of active ingredients and improves the absorption of active ingredients and enhances the effect of active ingredients. Nanoparticles can effectively control the release rate of active ingredients. The nanoparticle-loaded active ingredient can also shield the active ingredient from contact with the enzyme liquid or acid-base solution in the body, and protect the active ingredient from being degraded by enzyme or acid-base solution.

Before the 1990s, the materials of nanoparticles were mostly acrylic acid derivatives, and most of these materials were hydrophobic, and the ability to carry hydrophilic active ingredients was low. After the 1990s, Akashi et al. developed a series of grafted nanoparticles with a hydrophobic core and a hydrophilic surface, which improved the hydrophilicity of the nanoparticles and the ability to carry hydrophilic active ingredients (Oral peptide using nanoparticles composed of novel graft copolymers having Hydrophobic backbone and hydrophilic branches, Int. J. Pharm., 1997, 149:93-106). Stieneker et al. have developed amino alkyl methacrylic acid series of hydrophilic nanoparticles. Several nanoparticles have strong positive charges, which are easy to adsorb negatively charged hydrophilic DNA and protein drugs, and improve the delivery of hydrophilic active ingredients. (Preparation, characterization and cytotoxicity of methylmethacrylate copolymer nanoparticles with a permanent positive surface charge, Int.J.Pharm., 1997, 157: 189-198). The existing nanoparticles have the disadvantages of low loading of active ingredients, burst release and poor stability.

Contents of the invention

The object of the present invention is to provide a block copolymer nanoparticle with a hydrophobic core and a hydrophilic surface and a preparation method thereof with a high amount of loaded active ingredients and good stability, and to provide such block copolymers with a hydrophobic core and a hydrophilic surface. The application of copolymer nanoparticles to overcome the deficiencies and defects of the prior art.

Design of the present invention is as follows:

A diblock copolymer is obtained by copolymerization of hydrophobic methyl methacrylate and hydrophilic methacrylic acid derivatives. After purification, it is dispersed in water to form amphiphilic nanoparticles, and its hydrophilic chain is relatively short. Chitosan has good biocompatibility and safety, and is a good material for preparing nanoparticles. However, chitosan nanoparticles are prone to precipitation and aggregation under physiological environmental conditions, which seriously affect the absorption of active ingredients. In order to improve the stability of chitosan nanoparticles and obtain nanoparticles with longer hydrophilic chains, the present invention adopts the principle of free radical reaction to modify chitosan with acrylic acid derivatives or methacrylic acid derivatives, and then through copolymerization A tri-block copolymer is obtained, and nanoparticles are obtained after purification.

Technical scheme of the present invention is as follows:

Nanoparticles with a hydrophobic core and a hydrophilic surface proposed by the present invention are composed of the following two polymers: a hydrophobic polymer block of polyalkyl acrylate or polyalkyl methacrylate and a hydrophilic unsaturated A monomer or a polymer-modified chitosan hydrophilic polymer block formed from the hydrophilic unsaturated monomer.

Wherein the weight ratio of hydrophilic unsaturated monomer to chitosan is in the range of 20:80 to 80:20, alkyl acrylate or alkyl methacrylate and hydrophilic unsaturated monomer-chitosan The weight ratio of the copolymer or the polymer-chitosan copolymer formed from the hydrophilic unsaturated monomer is in the range of 90:10 to 50:50.

Said alkyl methacrylate is one of methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate, isobutyl methacrylate and hexyl methacrylate or more than one.

Said alkyl acrylate is one or more of methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, isobutyl acrylate and hexyl acrylate.

Said hydrophilic unsaturated monomers are acrylic acid, methacrylic acid, acrylates, methacrylates, salts or acids of acrylates, salts or acids of methacrylates, amides of acrylic acid Amides of methacrylic acid, N-alkylamides of acrylic acid, N-alkylamides of methacrylic acid, salts and acids of N-alkylacrylic acid amides, N-alkylmethacrylic acid One or more of salts and acids of amides, acrylamide, acrylamide derivatives, methacrylamide, and methacrylamide derivatives.

Commonly used hydrophilic unsaturated monomers are methacrylic acid, acrylamide, N-isopropylacrylamide, methacryloyloxyethyltrimethylammonium chloride (TMAEMC), dimethylaminomethacrylate One or more of ethyl ester (DMAEMC), 3-sulfopropyl-acrylic acid potassium salt.

The nanoparticle with hydrophobic core and hydrophilic surface of the present invention has a particle diameter of 100-250nm.

The present invention has the nanoparticle of hydrophobic core, hydrophilic surface, and its preparation method is as follows:

(1) dissolving chitosan in 1% acetic acid, heating to 60-75°C, adding an initiator, and adding a hydrophilic unsaturated monomer after 10-60 minutes to form a graft copolymer;

(2) After 10 to 90 minutes, add hydrophobic alkyl acrylate or methacrylate, and react for 2 to 24 hours to obtain an amphoteric tri-block copolymer;

(3) Purifying the above-mentioned tri-block copolymer to obtain tri-block amphiphilic nanoparticles with a hydrophobic core and a hydrophilic surface.

Wherein the weight ratio of hydrophilic unsaturated monomer to chitosan is in the range of 20:80 to 80:20, alkyl acrylate or alkyl methacrylate and hydrophilic unsaturated monomer-chitosan The weight ratio of the copolymer or the polymer-chitosan copolymer formed from the hydrophilic unsaturated monomer is in the range of 90:10 to 50:50.

Said alkyl methacrylate is one of methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate, isobutyl methacrylate and hexyl methacrylate or more than one.

Said alkyl acrylate is one or more of methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, isobutyl acrylate and hexyl acrylate.

Said hydrophilic unsaturated monomers are acrylic acid, methacrylic acid, acrylates, methacrylates, salts or acids of acrylates, salts or acids of methacrylates, amides of acrylic acid Amides of methacrylic acid, N-alkylamides of acrylic acid, N-alkylamides of methacrylic acid, salts and acids of N-alkylacrylic acid amides, N-alkylmethacrylic acid One or more of salts and acids of amides, acrylamide, acrylamide derivatives, methacrylamide, and methacrylamide derivatives.

Commonly used hydrophilic unsaturated monomers are methacrylic acid, acrylamide, N-isopropylacrylamide, methacryloyloxyethyltrimethylammonium chloride (TMAEMC), dimethylaminomethacrylate One or more of ethyl ester (DMAEMC), 3-sulfopropyl-acrylic acid potassium salt.

Said initiator is ammonium persulfate or potassium persulfate. Its dosage is 0.01-0.2% (g/ml) of the reaction system.

When carrying out the reaction, chitosan, alkyl methacrylate and hydrophilic unsaturated monomer can be added in no particular order.

The molecular weight of the triblock copolymer of the present invention can be determined by the input monomer amount, reaction time and initiator concentration. Other parameters, such as reaction temperature, addition method of hydrophilic polymer, use of nitrogen, reaction time, etc., can be adjusted as required.

The present invention investigates the effects of hydrophilic monomer concentration, hydrophobic monomer concentration, total monomer concentration, initiator concentration, pH, reaction time, etc. on nanoparticles, and has prepared several kinds of stable nanoparticles.

Purification steps in the preparation of nanoparticles include techniques known to those skilled in the art. After dialysis or ultrafiltration, the nanoparticle suspension obtained can be used directly, or it can be separated or collected by any suitable physical means known per se, for example: by filtration, concentration, density gradient centrifugation, precipitation, adding Salt or freeze-dried, etc.

Impurities (salts) and solvents can be removed by any suitable physical separation treatment, eg, by dialysis, filtration, pH change, chromatography or distillation and the like.

The tri-block polymer of the present invention spontaneously forms nanoparticles in aqueous solution, and the nanoparticles can form powdery solids or stable colloidal suspensions in physiological media.

The nanoparticles of the present invention can be used as carriers of active ingredients. The nanoparticle colloidal suspension and/or powdery solid containing the present invention may include at least one of the following active ingredients:

(1) Proteins and peptides: insulin, hemoglobin, albumin, cytochrome, interferon, antigen, antibody, erythropoietin, growth hormone, interleukin, colony-stimulating factor and other conditional growth factors.

(2) Vaccine: alone or in combination with at least one antigen.

(3) Polysaccharides: especially choose heparin.

(4) Nucleic acid: RNA, DNA, oligonucleotide and polynucleotide.

(5) Non-peptide-protein molecules belonging to different types of anticancer chemotherapy, especially anthracyclines, doxorubicin, colchicine, taxanes, etc.

(6) A mixture of the above-mentioned various active ingredients.

The nanoparticle colloidal suspension of the present invention can be filtered through a sterilizing filter to obtain a sterile injectable or oral medicinal liquid, which is convenient and economical. Nanoparticles loaded with active ingredients are used for the production of eg pharmaceutical products of the type controlled release active ingredient systems. They may be pharmaceutical products administered by oral or nasal, vaginal, ophthalmic, subcutaneous, intravenous, intramuscular, intradermal, intraperitoneal, intracerebral, etc. routes.

The nanoparticles of the invention can be used for the production of special products for nutrition, plant protection or cosmetics. Cosmetic applications such as the combination of nanoparticles and active ingredients can be used transdermally.

The advantages of the present invention are:

(1) the nanoparticles of the present invention are relatively stable under physiological conditions, avoiding the easy flocculation and precipitation of chitosan nanoparticles, and the hydrophilic chains of the nanoparticles of the present invention are longer, which is conducive to improving the capacity of carrying hydrophilic active ingredients. quantity.

(2) The synthesis route of the triblock copolymer of the present invention is easy, the purification process is simple and convenient, and the source of the monomer material is convenient.

(3) The copolymer synthesized in aqueous solution can spontaneously form nanoparticles without adding organic solvents, surfactants and the like.

(4) The particle diameters of the nanoparticles of the present invention are all less than 250nm, and the polydispersity indices are all less than 0.1, indicating that the nanoparticles have a smaller particle diameter and a narrower distribution range. The nanoparticles of the present invention have strong surface charge (Zeta potential), are relatively stable under physiological environmental conditions, and are not easy to produce aggregation and precipitation.

(5) The charged nanoparticles with a hydrophilic surface of the present invention are not easily recognized by the endothelial phagocytosis system, which can increase the circulation time of the active ingredient in the body and enhance the active effect. For example, the epithelial cells of tumors and other lesions are in a leaky state. Due to the long circulation of nanoparticles in the body, the chances of the drugs carried by them to enter the lesions increase.

(6) The chitosan in the nanoparticle of the present invention has an adhesion effect, which can increase the concentration difference of the active ingredient between the surface of the mucous membrane and the inner layer of the mucous membrane, which is beneficial to the diffusion of the active ingredient and improves the effect of the active ingredient.

(7) Certain groups (such as carboxyl groups) on acrylic acid derivatives or methacrylic acid derivatives can combine with some enzymes to destroy the active center of the enzyme, thereby protecting nucleic acid and protein drugs.

(8) The amphiphilic nanoparticles in the present invention have longer hydrophilic chains, and acrylic acid derivatives, methacrylic acid derivatives and chitosan have a certain charge, and the hydrophilic active ingredients do not need to undergo high-speed centrifugation. , ultrasonic treatment, organic solvents, surfactants, emulsification, evaporation and other special treatments can be freely adsorbed on the surface of nanoparticles without destroying the activity of active ingredients.

(9) The combination of the drug and the nanoparticle is relatively strong, and no sudden release phenomenon will occur in the body. The active ingredient can be slowly released from the nanoparticle, which plays a role in slow release and reducing the toxicity of the active ingredient.

(10) By changing the structure of the copolymer, the combination and release of active ingredients can be effectively controlled.

Detailed ways

Example 1

Add 0.75 grams of chitosan to 70ml of 1% acetic acid, heat to 60°C, stir until the chitosan is completely dissolved, add 1.5 grams of methyl methacrylate and 0.0175 grams of ammonium persulfate, react for 2 hours, and dialyze for 48 hours , lyophilized into powder, dispersed in water to form diblock nanoparticles (CM nanoparticles), the particle size is 152.6nm.

Example 2

Add 0.75 grams of chitosan to 70ml of 1% acetic acid, heat to 65°C, stir until the chitosan is completely dissolved, add 1.5 grams of n-butyl methacrylate and 0.02 grams of ammonium persulfate, react for 3 hours, and dialyze for 72 Hours, freeze-dried into powder, dispersed in water to form diblock nanoparticles with a particle size of 187.4nm.

Example 3

Add 1 gram of chitosan to 95ml of 1% acetic acid, heat to 70°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.1 gram of potassium persulfate, and add 1 gram of quaternary ammonium methacrylate after 10 minutes Salt, add 1.5 grams of methyl methacrylate after 30 minutes, react for 18 hours, dialyze for 96 hours, freeze-dry to powder, disperse in water to form triblock nanoparticles (CTM nanoparticles), particle size is 169.2nm.

Example 4

Add 0.75 grams of chitosan to 70ml of 1% acetic acid, heat to 70°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.06 grams of ammonium persulfate, and add 1 gram of tertiary ammonium methacrylate after 20 minutes Salt, add 1.2 grams of methyl methacrylate after 30 minutes, react for 24 hours, dialyze for 56 hours, freeze-dry to powder, disperse in water to form triblock nanoparticles (CDM nanoparticles), particle size is 139.4nm.

Example 5

Add 0.5 grams of chitosan to 95ml of 1% acetic acid, heat to 75°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.1 grams of ammonium persulfate, and add 0.5 grams of quaternary ammonium methacrylate after 10 minutes Salt, 0.75 g of methyl methacrylate was added after 60 minutes, reacted for 16 hours, dialyzed for 72 hours, freeze-dried into powder, dispersed in water, and formed triblock nanoparticles (CTM nanoparticles), with a particle size of 154.7nm.

Example 6

Add 1 gram of chitosan to 95ml of 1% acetic acid, heat to 65°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.1 gram of ammonium persulfate, and add 1 gram of quaternary ammonium methacrylate after 20 minutes After 30 minutes, 1.8 g of isobutyl methacrylate was added, reacted for 24 hours, dialyzed for 96 hours, freeze-dried into powder, dispersed in water, and formed triblock nanoparticles with a particle size of 189.5 nm.

Example 7

Add 0.75 grams of chitosan to 95ml of 1% acetic acid, heat to 72°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.09 grams of potassium persulfate, and add 1.2 grams of quaternary ammonium methacrylate after 30 minutes After 30 minutes, add 2 grams of methyl acrylate, react for 14 hours, dialyze for 60 hours, freeze-dry to powder, and disperse in water to form triblock nanoparticles with a particle size of 166.8nm.

Example 8

Add 1 gram of chitosan to 95ml of 1.5% acetic acid, heat to 65°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.12 grams of ammonium persulfate, and add 0.5 grams of tertiary ammonium methacrylate after 20 minutes salt, after 50 minutes, add 1 gram of n-butyl methacrylate, react for 15 hours, dialyze for 80 hours, freeze-dry to powder, disperse in water, and form triblock nanoparticles with a particle size of 192.3nm.

Example 9

Add 0.75g of chitosan to 95ml of 1.5% acetic acid, heat to 75°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.1g of ammonium persulfate, and add 0.75g of tertiary ammonium methacrylate after 20 minutes Salt, after 30 minutes, add 1 gram of isobutyl methacrylate, react for 12 hours, dialyze for 96 hours, freeze-dry to powder, disperse in water, and form triblock nanoparticles with a particle size of 154.2nm.

Example 10

Add 0.75 grams of chitosan to 95ml of 1% acetic acid, heat to 70°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.09 grams of ammonium persulfate, and add 0.5 grams of tertiary ammonium methacrylate after 20 minutes After 30 minutes, add 1.2 g of methyl acrylate, react for 8 hours, dialyze for 60 hours, freeze-dry to powder, and disperse in water to form triblock nanoparticles with a particle size of 147.9 nm.

Example 11

Add 0.375 grams of chitosan to 70ml of 1% acetic acid, heat to 75°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.06 grams of ammonium persulfate, and add 0.5 grams of tertiary methacrylic acid after 40 minutes Ammonium salt, add 0.6 g of methyl methacrylate after 60 minutes, react for 8 hours, dialyze for 72 hours, freeze-dry to powder, disperse in water to form triblock nanoparticles (CDM nanoparticles), particle size is 133.6nm .

Example 12

Add 1 gram of chitosan to 95ml of 1% acetic acid, heat to 68°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.1 gram of ammonium persulfate, and add 1 gram of quaternary ammonium methacrylate after 20 minutes Salt, after 30 minutes, add 2 grams of methyl methacrylate, react for 24 hours, dialyze for 68 hours, freeze-dry to powder, disperse in water to form triblock nanoparticles (CTM nanoparticles), particle size is 176.4nm .

Example 13

Add 0.75 grams of chitosan to 70ml of 1% acetic acid, heat to 75°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.06 grams of ammonium persulfate, and add 1 gram of tertiary ammonium methacrylate after 30 minutes After 40 minutes, add 1.8 grams of methyl methacrylate, react for 12 hours, dialyze for 56 hours, freeze-dry to powder, disperse in water, and form triblock nanoparticles (CDM nanoparticles), with a particle size of 145.2nm.

Example 14

Add 1.2 grams of chitosan to 95ml of 1% acetic acid, heat to 65°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.1 grams of ammonium persulfate, and add 1.2 grams of quaternary ammonium methacrylate after 30 minutes Salt, after 30 minutes, add 1.5 grams of methyl methacrylate, react for 24 hours, dialyze for 80 hours, lyophilize into powder, disperse in water, and form triblock nanoparticles (CTM nanoparticles), with a particle size of 149.8nm .

Example 15

Add 1 gram of chitosan to 95ml of 1% acetic acid, heat to 70°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.075 grams of ammonium persulfate, and add 1 gram of quaternary ammonium methacrylate after 30 minutes Salt, 1.5 g of methyl methacrylate was added after 30 minutes, reacted for 24 hours, and dialyzed for 75 hours to form triblock nanoparticles (CTM nanoparticles) with a particle size of 171.5 nm.

Example 16

Add 0.75 grams of chitosan to 70ml of 1% acetic acid, heat to 72°C, stir until the chitosan is completely dissolved, blow in nitrogen, add 0.06 grams of ammonium persulfate, and add 0.75 grams of tertiary ammonium methacrylate after 20 minutes After 40 minutes, add 1.2 grams of methyl methacrylate, react for 16 hours, and dialyze for 96 hours to form triblock nanoparticles (CDM nanoparticles) with a particle size of 141.8nm.

Example 17

Regulate the pH of CM (embodiment 1), CDM (embodiment 12), CTM (embodiment 13) nanoparticle solution with HCl and NaOH solution to be 3,4,5,6,7,8,9,10,11 respectively , 12, 13 and 14 to investigate the stability of nanoparticles, the results are shown in Table 1 below:

When table 1 is at different pH, the stability of nanoparticles pH CM CDM CTM 3 Stablize Stablize Stablize 4 Stablize Stablize Stablize 5 Stablize Stablize Stablize 6 Stablize Stablize Stablize 7 slow precipitation Stablize Stablize 8 slow precipitation Stablize Stablize 9 slow precipitation Stablize Stablize 10 slow precipitation Stablize Stablize 11 Precipitate immediately slow precipitation Stablize 12 Precipitate immediately slow precipitation Stablize 13 Precipitate immediately Precipitate immediately Stablize 14 Precipitate immediately Precipitate immediately slow precipitation

It can be seen from Table 1 that a single chitosan nanoparticle produces flocculation and precipitation when the pH is greater than 6, and is unstable in a physiological environment, while the nanoparticle of the present invention is relatively stable under physiological conditions.

Example 18

Mix the 1 mg/ml insulin PBS solution with 2% CM (Example 1), CDM (Example 12), CTM (Example 13) nanoparticle colloidal suspension, shake at 37°C for 5 hours, and centrifuge at 15,000rpm for 50 Minutes, take the supernatant, use the Lowry method to measure the content of insulin in the supernatant, and calculate the encapsulation efficiency. The results are shown in Table 2 below.

Table 2 Encapsulation efficiencies of insulin loaded on different nanoparticles Nanoparticles Encapsulation rate (%) CM nanoparticles 65.7 CDM nanoparticles 100 CTM nanoparticles 100

Example 19

Normal SD rats were given intragastric administration of CM (embodiment 1), CDM (embodiment 12), CTM (embodiment 13) nanoparticle colloid suspension (100U/kg) loaded with insulin, respectively at 0, 1, 2 , 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours, take 0.2ml of blood from the tail vein, after the blood coagulates, centrifuge at 12,000rpm for 4 minutes, take 20ul of serum, and measure it by glucose oxidase method Blood sugar level.

Table 3 The hypoglycemic effect of different insulin-loaded nanoparticles Time for blood sugar to return to basal level (hours) insulin solution 1 CM Nanoparticle Insulin Solution 6 CDM Nanoparticle Insulin Solution 10 CTM nanoparticle insulin solution 16

It can be seen from Table 3 that CDM and CTM nanoparticles have good sustained-release effects.

Example 20

Superoxide dismutase (SOD) is easily inactivated, which limits its use in cosmetics. Mix nanoparticles CDM (Example 12) and CTM (Example 13) with SOD, homogeneously emulsify, place at 70°C for 1 hour, and measure SOD activity by using pyrogallol aerobic method (325nm). The results are shown in Table 4.

The impact of table 4 nanoparticles on the stability of SOD active(%) SOD 51.7 CDM nanoparticles + SOD 88.4 CTM nanoparticles + SOD 89.2

It can be seen from Table 4 that CDM and CTM nanoparticles have the effect of stabilizing SOD

Claims (11)

1. A nanoparticle with a hydrophobic core and a hydrophilic surface, characterized in that it consists of the following two polymers: a hydrophobic polymer block of polyalkylacrylate or polyalkylmethacrylate and a hydrophilic The hydrophilic polymer block of chitosan modified by the polymer of the unsaturated monomer or the hydrophilic unsaturated monomer formed; Wherein, the weight ratio of the hydrophilic unsaturated monomer and chitosan is in In the range of 20:80 to 80:20, alkyl acrylate or alkyl methacrylate and hydrophilic unsaturated monomer-chitosan copolymer or polymer formed by the hydrophilic unsaturated monomer - The weight ratio of the chitosan copolymer is in the range of 90:10 to 50:50. 2. The nanoparticle according to claim 1, characterized in that said alkyl methacrylate is methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate, methyl methacrylate, One or more of isobutyl acrylate and hexyl methacrylate; said alkyl acrylate is methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, isobutyl acrylate and acrylic acid One or more of hexyl esters. 3. The nanoparticle according to claim 1, characterized in that said hydrophilic unsaturated monomer is acrylic acid, methacrylic acid, acrylates, methacrylates, acrylate salts or acids , salts or acids of methacrylates, amides of acrylic acid, amides of methacrylic acid, N-alkylamides of acrylic acid, N-alkylamides of methacrylic acid, N-alkylamides of acrylic acid One or one of salts and acids of methacrylic acid N-alkylamides, acrylamide, acrylamide derivatives, methacrylamide, methacrylamide derivatives above. 4. The nanoparticle according to claim 3, characterized in that the hydrophilic unsaturated monomer used is acrylamide, N-isopropylacrylamide, methacryloyloxyethyltrimethylammonium chloride, One or more of dimethylaminoethyl methacrylate and 3-sulfopropyl-acrylic acid potassium salt. 5. Nanoparticles according to claims 1-4, characterized in that the particle size is 100-250nm. 6. A method for preparing nanoparticles with a hydrophobic core and a hydrophilic surface, characterized in that the specific steps are as follows: (1) dissolving chitosan in 1% acetic acid, heating to 60-75°C, adding an initiator, and adding a hydrophilic unsaturated monomer after 10-60 minutes to form a graft copolymer; (2) After 10 to 90 minutes, add hydrophobic alkyl acrylate or methacrylate, and react for 2 to 24 hours to obtain an amphoteric tri-block copolymer; (3) purifying the above-mentioned tri-block copolymer to obtain tri-block amphiphilic nanoparticles with a hydrophobic core and a hydrophilic surface; Wherein, the weight ratio of hydrophilic unsaturated monomer to chitosan is in the range of 20:80 to 80:20, alkyl acrylate or alkyl methacrylate and hydrophilic unsaturated monomer-chitosan The weight ratio of the sugar copolymer or the polymer-chitosan copolymer formed from the hydrophilic unsaturated monomer is in the range of 90:10 to 50:50. 7. The method for preparing nanoparticles according to claim 6, characterized in that said alkyl methacrylate is methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate One or more of methacrylate, isobutyl methacrylate and hexyl methacrylate; said alkyl acrylate is methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, isobutyl acrylate and one or more of hexyl acrylate; said hydrophilic unsaturated monomers are acrylic acid, methacrylic acid, acrylates, methacrylates, salts or acids of acrylates, methyl Salts or acids of acrylates, amides of acrylic acid, amides of methacrylic acid, N-alkylamides of acrylic acid, N-alkylamides of methacrylic acid, N-alkylamides of acrylic acid One or more of salts and acids, salts and acids of N-alkylamides of methacrylic acid, acrylamide, acrylamide derivatives, methacrylamide, and methacrylamide derivatives. 8. The method for preparing nanoparticles according to claim 7, characterized in that the hydrophilic unsaturated monomer used is acrylamide, N-isopropylacrylamide, methacryloyloxyethyl trimethyl chloride One or more of ammonium, dimethylaminoethyl methacrylate, and 3-sulfopropyl-acrylic acid potassium salt. 9. The method for preparing nanoparticles according to claim 6, characterized in that said initiator is one of ammonium persulfate or potassium persulfate, and the dosage is 0.01-0.2% of the reaction system, g/ml. 10. The application of a nanoparticle with a hydrophobic core and a hydrophilic surface as an active ingredient carrier, and the active ingredient is at least one of the following: (1) Protein and polypeptide: one of insulin, hemoglobin, albumin, cytochrome, interferon, antigen, antibody, erythropoietin, growth hormone, interleukin and colony-stimulating factor; (2) Vaccine: alone or in combination with at least one antigen; (3) Polysaccharides: especially choose heparin; (4) Nucleic acids: RNA, DNA, oligonucleotides and polynucleotides; (5) Non-peptide-protein molecules belonging to different types of anticancer chemotherapy, especially one of anthracycline, doxorubicin, colchicine, taxanes. 11. The use of a nanoparticle with a hydrophobic core and a hydrophilic surface in special products for nutrition, plant protection or cosmetics.