Polymer drug-loaded particle capable of being adhered to intestinal inflammation region in targeted manner as well as preparation method and application of polymer drug-loaded particle

Abstract

The invention discloses a polymer drug-loaded particle for targeted adhesion to an intestinal inflammation area and a preparation method and application thereof.The method includes the steps that degradable polymer drug-loaded particles are subjected to surface modification through polycations and then added into a monomer solution of an adhesion layer, particle surface in-situ polymerization is initiated through ultraviolet irradiation, and a PAN adhesion layer is formed; the adhesion layer modified polymer drug-loaded particles are obtained. Wherein the polycation is used as a middle layer, so that the PAN adhesion layer can be successfully modified. Carboxyl in the adhesion layer enables the particles to present negative charges, meanwhile, succinimide ester can react with amino naturally existing on the surface of inflammatory intestinal tissue to generate an amide covalent bond, and finally targeted adhesion of the intestinal inflammation part is achieved. According to the adhesion strategy, the PAN can be effectively applied to the micro-nano-scale drug-loaded particles so as to enhance the adhesion of the micro-nano-scale drug-loaded particles in an intestinal tract damaged area, and a brand new thought is provided for treating inflammatory intestinal tracts.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology and relates to a polymer drug-loaded particle, in particular to a polymer drug-loaded particle targeted to adhere to an intestinal inflammatory area and a preparation method and application thereof. Background Art

[0002] Most of the existing inflammatory bowel disease (IBD) therapeutic drugs are administered by systemic administration, which results in insufficient concentration of drugs in the local intestinal damaged area, and is accompanied by more systemic side effects, such as neurotoxicity and nephrotoxicity. In order to improve the concentration of drugs in the local intestinal damaged area, researchers have developed a series of drug delivery systems for the local intestinal damaged area, wherein degradable polymers such as polylactic-co-glycolic acid (PLGA) are widely used as a carrier material with good biocompatibility for drug encapsulation and sustained release. However, due to its hydrophobicity and inertness, there is a lack of sufficient interaction between degradable polymer particles and tissues, which affects the retention and therapeutic effect of drugs in the damaged area (Endothelial and vascular smooth muscle cell function on poly (lactic-co-glycolic acid) with nano-structured surface features. Biomaterials 2004, 25 (1), 53-61.), and existing degradable polymer particles have limitations in the treatment of inflammatory bowel disease (IBD), particularly lack of specific interaction between particles and damaged intestinal tissue. Although existing biodegradable polymer particles have certain physical embedding effects and good biocompatibility, they are difficult to achieve stable tissue adhesion and drug retention in the complex intestinal environment due to their hydrophobicity and biological inertness. Therefore, an improved method is needed to enhance the interaction between biodegradable polymers and damaged intestinal tissues. Summary of the invention

[0003] The purpose of the present invention is to provide a polymer drug-loaded particle with targeted adhesion to the intestinal inflammation area and its preparation method and application in view of the deficiencies of the prior art. The method improves the adhesion of the particles to the damaged intestinal tissue by surface modification of the degradable polymer drug-loaded particles, introducing covalent interactions, and designing an adhesion strategy capable of forming chemical bonds by utilizing naturally existing amino groups and other groups on the surface of inflammatory intestinal tissue, thereby achieving targeted adhesion to the intestinal inflammation area.

[0004] The technical solution adopted by the present invention is as follows:

[0005] A method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammation areas comprises the following steps:

[0006] The desired loaded drug and the degradable polymer are dissolved in an organic solvent to form an organic phase, and the organic phase is added to the first emulsifier aqueous solution, and ultrasonically emulsified to form colostrum; the colostrum is then added to the second emulsifier aqueous solution, stirred and volatilized overnight, centrifuged, washed, and then freeze-dried to obtain degradable polymer drug-loaded particles;

[0007] Adding the degradable polymer drug-loaded particles into the polycation solution, stirring and incubating, centrifuging and washing, and freeze-drying to obtain polymer particles modified with the intermediate layer;

[0008] The polymer particles modified by the intermediate layer are added to the monomer solution of the adhesion layer, which is a mixed solution containing acrylic acid AA and succinimidyl ester NHS, and a photoinitiator and a cross-linking agent are added, and in situ polymerization is carried out under ultraviolet irradiation. After centrifugal washing, freeze-drying is performed to obtain the drug-loaded particles that target and adhere to the intestinal inflammation area.

[0009] Further, the degradable polymer is one or more of polylactic acid PLA, polylactic acid-glycolic acid copolymer PLGA, polyglycolic acid PGA, polycaprolactone PCL, polyglycolic acid PELA, and polyamino acid; further, the organic solvent is one or more of dichloromethane, chloroform, benzene, toluene, ethyl acetate, and acetone;

[0010] Furthermore, the emulsifier is one or more of Tween 20, Tween 80, PVA, polyoxyethylene (16) sorbitan monotoluene ester, polyoxyethylene (10) sorbitan monolaurate, polyoxyethylene (20) sorbitan dioleate, polyoxyethylene (18) sorbitan monostearate, polyoxyethylene (3,8) glycerol monolaurate, sodium oleate, sodium rosinate, C14-18 alkyl sodium sulfate, sodium dodecylbenzene sulfonate, and dialkyl sulfosuccinate.

[0011] Furthermore, the mass concentration of the first emulsifier aqueous solution is 0.5% to 5%, the mass concentration of the second emulsifier aqueous solution is 0.1% to 2%, and the concentration ratio of the first emulsifier aqueous solution to the second emulsifier aqueous solution is preferably 1.5 to 10:1.

[0012] Furthermore, the volume ratio of the organic phase to the first emulsifier aqueous solution is 1:2-20, and the volume ratio of the colostrum to the second emulsifier aqueous solution is 1:2-10.

[0013] Furthermore, the polycation is one or more of polyethyleneimine, chitosan, methacrylamide chitosan, gelatin, and peptides. The concentration of the polycation solution is 0.1-20 mg / mL.

[0014] Furthermore, in the monomer solution of the adhesion layer, the concentration of acrylic acid is 0.1-0.8 mol / L, and the molar ratio of AA to NHS is preferably 1-30:1. When it is lower than this range, the obtained particles are easy to agglomerate into white lumps, which is not conducive to subsequent treatment and application. When it is higher than this range, the final product has a poor targeting effect and is also not conducive to application. The molar ratio of the photoinitiator to the monomer is 1:50-300, and the molar ratio of the crosslinker to the monomer is 1:50-300.

[0015] Furthermore, the drug can generally be one or more of tacrolimus, budesonide, dexamethasone, tofacitinib, upadacitinib, and rapamycin.

[0016] The present invention modifies the surface of the drug-loaded degradable polymer particles with positively charged polycations by electrostatic adsorption, then adds the polycation-modified polymer particles to the monomer solution of the adhesion layer (acrylic acid, succinimidyl ester or acrylic acid-N-succinimidyl ester, initiator, cross-linking agent, etc.), and ultraviolet irradiation triggers in-situ polymerization of the particle surface to form a PAN (PAA-NHS abbreviation, polyacrylic acid-N-hydroxysuccinimide) adhesion layer to obtain polymer particles modified with an adhesion layer. The polycation serves as an intermediate layer, so that the PAN adhesion layer can be successfully modified. The carboxyl groups in the adhesion layer make the particles present a negative charge and can bind to a large number of positively charged proteins accumulated in the inflammatory site. At the same time, the succinimidyl ester (NHS) can react with the naturally existing amino groups on the surface of the inflammatory intestinal tissue to form an amide covalent bond, and finally achieve targeted adhesion to the intestinal inflammatory site. This adhesion strategy effectively applies PAN to micro-nano-level drug-loaded particles to enhance their adhesion in damaged areas of the intestine, providing a new idea for the treatment of inflammatory bowel.

[0017] The beneficial effects of the present invention are at least as follows:

[0018] (1) The preparation method of introducing an intermediate layer and in-situ polymerization provided by the present invention realizes the modification of the adhesion layer on the surface of the degradable polymer particles through electrostatic interaction and ultraviolet light-induced in-situ polymerization. The preparation process is simple and efficient, biosafe, and has universal applicability, and is applicable to various drugs, various negatively charged surface particles, and various adhesion application requirements, which is very beneficial to production and application.

[0019] (2) The present invention significantly improves the adhesion and retention effect of polymer particles on inflammatory intestinal tissue by introducing an adhesion coating on the surface of degradable polymer particles, thereby optimizing the drug delivery efficiency. Experimental results show that in a mouse acute colitis model, polymer particles modified with a PAN adhesion layer can effectively retain in the damaged intestinal area, and the drug concentration in the damaged tissue is about 15 times higher than that of unmodified particles (215.4±18.2ng / g vs 14.9±3.2ng / g).

[0020] (3) The present invention introduces an adhesive coating on the surface of the degradable polymer particles, effectively reducing the side effects of drug delivery and ensuring the safety of drug application. No significant systemic toxicity was observed during the treatment process, and liver and kidney function indicators such as serum ALT and creatinine levels remained within the normal range, indicating that the drug delivery system of the present invention has good biosafety and clinical application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Transmission electron microscope image and laser confocal microscope image of PLGA@PEI@PAN particles obtained in Example 1.

[0022] Figure 2 This is a comparison chart of the zeta potential data of PLGA@PEI@PAN, PLGA and PLGA@PEI particles obtained in Example 1, Comparative Example 1 and Comparative Example 2.

[0023] Figure 3 This is a comparison chart of the infrared transmission spectra of PLGA@PEI@PAN and PLGA particles obtained in Example 1 and Comparative Example 1.

[0024] Figure 4 This is a laser confocal microscope image of the PLGA@PAN particles obtained in Comparative Example 3.

[0025] Figure 5 Comparison of the intestinal tissue adhesion capabilities of PLGA@PEI@PAN (c, d) and PLGA (a, b) particles obtained in Application Example 1.

[0026] Figure 6 This is a bar chart showing the drug delivery and retention capabilities of the PLGA@PEI@PAN particles obtained in Application Example 1. DETAILED DESCRIPTION

[0027] The technical solution of the present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments.

[0028] Example 1

[0029] Step 1: Preparation of PLGA drug-loaded particles: 15 mg of tacrolimus and 400 mg of PLGA were dissolved in 4 mL of dichloromethane to form an organic phase. The solution was slowly added to 20 mL of 1% polyvinyl alcohol (PVA) aqueous solution and emulsified using an ultrasonic device (ultrasonic power 50 W, cycle 10 seconds on, 3 seconds off) to form colostrum. Subsequently, the colostrum was added to 60 mL of 0.5% PVA solution and stirred to evaporate overnight. Finally, centrifuged (10,000 rpm, 3 minutes) and washed at least 3 times, freeze-dried and stored to obtain PLGA drug-loaded particles.

[0030] Step 2: Add PLGA particles to 40 mL of 0.5 mg / mL PEI solution, stir and incubate for 4 hours, centrifuge and wash 3 times, freeze-dry and store to obtain PEI-modified PLGA particles (PLGA@PEI).

[0031] Step 3: PLGA@PEI particles were added to a 5 mL mixed solution containing AA (150 μL, 2.2 mmol) and NHS (15 mg, 0.09 mmol), and photoinitiator I2959 (2.5 mg) and crosslinker N,N'-methylenebisacrylamide (3 mg) were added at the same time. The mixture was then exposed to ultraviolet light (365 nm, 120 mW / cm 2 ) for 300 seconds to induce in situ polymerization, and then the particles were washed by centrifugation for 3 times and freeze-dried to obtain PLGA particles modified with an adhesion layer (PLGA@PEI@PAN).

[0032] To verify the successful preparation of the adhesion layer modified particles, morphological tests were performed: the PLGA@PEI@PAN prepared in Example 1 was subjected to transmission electron microscopy (TEM) testing, and the PAN adhesion layer was labeled with 7-amino-4-methylcoumarin, and the PLGA particle core was labeled with Nile red, and laser confocal testing was performed.

[0033] Results Figure 1 , indicating that PLGA@PEI@PAN has a core-shell structure and adhesion layer modified particles were successfully prepared.

[0034] In order to verify the effectiveness of modifying the intermediate layer of the particles by the adhesion layer, a zeta potential test was performed: the PLGA@PEI@PAN prepared in Example 1 was dispersed in water at a concentration of 0.1 mg / mL, and a zeta potential test was performed using a nanoparticle size analyzer (DLS).

[0035] Results Figure 2 , indicating that the surface charge of PLGA@PEI@PAN changes from negative to positive to negative during the preparation process, which corresponds to the charge properties of PLGA, PEI and PAN. The results prove that the intermediate layer can effectively realize the charge transition from negative to positive on the surface of PLGA particles, which is an important guarantee for the adsorption of negatively charged monomers for in situ polymerization.

[0036] In order to verify whether the adhesion layer modified particles contain NHS active groups and have the reaction activity with amino groups, an infrared test of the particles was carried out: the PLGA@PEI@PAN prepared in Example 1 was pressed into tablets using potassium bromide and then subjected to infrared testing.

[0037] Results Figure 3The infrared spectrum shows that compared with the PLGA particles prepared in the upper figure of the comparative example 1 without the adhesion layer modification, the adhesion layer modified particles PLGA@PEI@PAN prepared in the lower figure of the embodiment 1 have an average wavelength of 1367 cm -1 The enhanced infrared peak appears at , which corresponds to the stretching vibration peak of CN, which is also the characteristic peak of NHS group. The results show that the adhesion layer modified particles contain NHS active groups and have the reaction activity with amino groups.

[0038] Example 2

[0039] Step 1: Preparation of PLGA drug-loaded particles: 15 mg of tacrolimus and 400 mg of PLGA were dissolved in 4 mL of dichloromethane to form an organic phase. The solution was slowly added to 20 mL of 1% polyvinyl alcohol (PVA) aqueous solution and emulsified using an ultrasonic device (ultrasonic power 50 W, cycle 10 seconds on, 3 seconds off) to form colostrum. Subsequently, the colostrum was added to 60 mL of 0.5% PVA solution and stirred to evaporate overnight. Finally, centrifuged (10,000 rpm, 3 minutes) and washed at least 3 times, freeze-dried and stored to obtain PLGA drug-loaded particles.

[0040] Step 2: Add PLGA particles to 40 mL of 10 mg / mL chitosan (CS) solution, stir and incubate for 4 hours, centrifuge and wash 3 times, freeze-dry and store to obtain PEI-modified PLGA particles (PLGA@CS).

[0041] Step 3: PLGA@CS particles were added to a 5 mL mixed solution containing AA (150 μL, 2.2 mmol) and NHS (15 mg, 0.09 mmol), and photoinitiator I2959 (2.5 mg) and crosslinker N,N'-methylenebisacrylamide (3 mg) were added at the same time. The mixture was then exposed to ultraviolet light (365 nm, 120 mW / cm 2 ) for 300 seconds to induce in situ polymerization reaction, and then the particles were washed by centrifugation for 3 times and freeze-dried to obtain adhesion layer-modified PLGA particles (PLGA@CS@PAN).

[0042] Comparative Example 1

[0043] Preparation of PLGA drug-loaded particles: 15 mg of tacrolimus and 400 mg of PLGA were dissolved in 4 mL of dichloromethane to form an organic phase. The solution was slowly added to 20 mL of 1% polyvinyl alcohol (PVA) aqueous solution and emulsified using an ultrasonic device (ultrasonic power 50 W, cycle 10 seconds on, 3 seconds off) to form colostrum. Subsequently, the colostrum was added to 60 mL of 0.5% PVA solution and stirred to evaporate overnight. Finally, centrifuged (10,000 rpm, 3 minutes) and washed at least 3 times, freeze-dried and stored to obtain PLGA drug-loaded particles.

[0044] Comparative Example 2

[0045] Step 1: Preparation of PLGA drug-loaded particles: 15 mg of tacrolimus and 400 mg of PLGA were dissolved in 4 mL of dichloromethane to form an organic phase. The solution was slowly added to 20 mL of 1% polyvinyl alcohol (PVA) aqueous solution and emulsified using an ultrasonic device (ultrasonic power 50 W, cycle 10 seconds on, 3 seconds off) to form colostrum. Subsequently, the colostrum was added to 60 mL of 0.5% PVA solution and stirred to evaporate overnight. Finally, centrifuged (10,000 rpm, 3 minutes) and washed at least 3 times, freeze-dried and stored to obtain PLGA drug-loaded particles.

[0046] Step 2: Add PLGA particles to 40 mL of 0.5 mg / mL PEI solution, stir and incubate for 4 hours, centrifuge and wash 3 times, freeze-dry and store to obtain PEI-modified PLGA particles (PLGA@PEI).

[0047] Comparative Example 3

[0048] Step 1: Preparation of PLGA drug-loaded particles: 120 mg of rapamycin and 400 mg of PLGA were dissolved in 4 mL of dichloromethane to form an organic phase. The solution was added to 20 mL of 1% polyvinyl alcohol (PVA) aqueous solution and emulsified using an ultrasonic device (ultrasonic power 50 W, cycle 10 seconds on, 3 seconds off) to form colostrum. Subsequently, the colostrum was added to 60 mL of 0.5% PVA solution and stirred to evaporate overnight. Finally, centrifuged (10,000 rpm, 3 minutes) and washed at least 3 times, freeze-dried and stored to obtain PLGA drug-loaded particles.

[0049] Step 2: Prepare a reaction solution with a molar ratio of AA:NHS = 4:1 and an acrylic acid monomer concentration of 0.49 mol / L: 200ul acrylic acid (2.92mmol), 8mg I2959, and 9.4mg NN-methylenebisacrylamide are added to 5600ul water, and 123.5mg acrylic acid-N-succinimidyl ester (0.73mmol) is dissolved in 200uL N,N-dimethylformamide and added to the above mixture.

[0050] Step 3: Add PLGA particles to the above 6 mL mixed solution and disperse them evenly by ultrasonic. Irradiate with UV light for 300 s to initiate polymerization, and obtain particles (PLGA@PAN) that are directly in situ UV-polymerized without an intermediate layer. After the polymerization is completed, centrifuge and wash at least three times. Freeze-dry and store at low temperature.

[0051] Morphological test was performed on particles that underwent in-situ polymerization directly after removing the intermediate layer: PLGA@PAN prepared in Comparative Example 3 was subjected to laser confocal test, wherein the blue fluorescent dye 7-amino-4-methylcoumarin was used to label the PAN adhesion layer, and the red fluorescent dye Nile red was used to label the PLGA particle core.

[0052] Results Figure 4 , showing that the PLGA@PAN particles are spherical, the core-shell structure is not obvious, and there is no obvious PAN adhesion layer on the particle surface. It can be seen that the preparation of the intermediate layer plays a very important role and necessity for the in-situ polymerization of the adhesion layer on the particle surface. After the introduction of the intermediate layer, it can be adsorbed on the PLGA particles and can effectively adsorb negatively charged monomers to make the local monomer concentration on the particle surface higher, which is conducive to the in-situ polymerization of monomers on the particle surface.

[0053] Application Example 1

[0054] To explore whether the modification of the adhesion layer can enhance adhesion to the intestinal inflammation site, the PLGA@PEI@PAN particles prepared in Example 1 and the PLGA particles prepared in Comparative Example 1 were subjected to tissue adhesion tests: To induce acute colitis, mice took 2.0% dextran sulfate sodium (DSS) in drinking water for 7 days, and then took normal drinking water for 5 days for recovery. One day after DSS administration, the mice took the same amount of PLGA or PLGA@PEI@PAN orally every day until they were sacrificed. The colon intestines and other organs of the mice were removed and small animal live imaging was performed, in which Nile red was used to label the PLGA@PEI@PAN prepared in Example 1 and the PLGA prepared in Comparative Example 1.

[0055] Results Figure 5 , small animal live imaging images show that compared with Figure 5 (a) PLGA particles prepared in Comparative Example 1 without modification of the adhesion layer, Figure 5 (c) The adhesion layer modified particles PLGA@PEI@PAN prepared in Example 1 have a stronger fluorescence signal in the intestine, indicating that the particles have better intestinal adhesion effect and tissue retention ability.

[0056] Application Example 2

[0057] To explore whether the adhesion layer modified particles can improve the drug retention effect, the PLGA@PEI@PAN particles prepared in Example 1 and the PLGA particles prepared in Comparative Example 1 were tested for drug concentration: the drug was loaded into PLGA@PEI@PAN and PLGA particles. To induce acute colitis, mice took 2.0% dextran sulfate sodium (DSS) in drinking water for 7 days and then took normal drinking water for 5 days for recovery. One day after DSS administration, mice received drug-loaded PLGA or PLGA@PEI@PAN particles every day until they were sacrificed. The colon intestines of the mice were removed, cut into small pieces, weighed, and homogenized with 0.5mL of saline using a T18ULTRA-TURRAX homogenizer (IKA Co., Ltd.). 2mL of acetonitrile was added to the homogenate, and then vortexed in an ice bath for 30 minutes. After centrifugation at 4000 rpm for 15 min at 4°C, the supernatant was dried and reconstituted in 100 μL of acetonitrile and then stored at -20°C until HPLC-MS analysis.

[0058] Results Figure 6 ,Compared to direct administration of free drugs, the drug-loaded adhesion layer modified particles PLGA@PEI@PAN have a higher drug concentration in the intestine, indicating that the particles have a good drug delivery effect, can effectively improve the drug utilization efficiency, and reduce the systemic side effects of ,administration.

[0059] The above-described embodiments are only some of the preferred solutions of the present invention, but they are not intended to limit the present invention. A person skilled in the relevant technical field may make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, any technical solution obtained by equivalent replacement or equivalent transformation falls within the protection scope of the present invention.

Claims

1. A method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammation areas, characterized in that: include: The desired loaded drug and the degradable polymer are dissolved in an organic solvent to form an organic phase, and the organic phase is added to the first emulsifier aqueous solution, and ultrasonically emulsified to form colostrum; the colostrum is then added to the second emulsifier aqueous solution, stirred and volatilized overnight, centrifuged, washed, and then freeze-dried to obtain degradable polymer drug-loaded particles; Adding the degradable polymer drug-loaded particles into the polycation solution, stirring and incubating, centrifuging and washing, and freeze-drying to obtain polymer particles modified with the intermediate layer; The polymer particles modified by the intermediate layer are added to the monomer solution of the adhesion layer, which is a mixed solution containing acrylic acid AA and succinimidyl ester NHS, and a photoinitiator and a cross-linking agent are added, and in situ polymerization is carried out under ultraviolet irradiation. After centrifugal washing, freeze-drying is performed to obtain the drug-loaded particles that target and adhere to the intestinal inflammation area.

2. The method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammation areas according to claim 1, characterized in that: The degradable polymer is one or more of polylactic acid PLA, polylactic acid-glycolic acid copolymer PLGA, polyglycolic acid PGA, polycaprolactone PCL, polyglycolic acid PELA, and polyamino acid.

3. The method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammation areas according to claim 1, characterized in that: The organic solvent is one or more of dichloromethane, chloroform, benzene, toluene, ethyl acetate and acetone.

4. The method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammation areas according to claim 1, characterized in that: The emulsifier is one or more of Tween 20, Tween 80, PVA, polyoxyethylene (16) sorbitan monotolate, polyoxyethylene (10) sorbitan monolaurate, polyoxyethylene (20) sorbitan dioleate, polyoxyethylene (18) sorbitan monostearate, polyoxyethylene (3,8) glycerol monolaurate, sodium oleate, sodium rosinate, C14-18 alkyl sodium sulfate, sodium dodecylbenzene sulfonate, and dialkyl sulfosuccinate.

5. The method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammation areas according to claim 1, characterized in that: The mass concentration of the first emulsifier aqueous solution is 0.5% to 5%, and the mass concentration of the second emulsifier aqueous solution is 0.1% to 2%.

6. The method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammation areas according to claim 1, characterized in that: The volume ratio of the organic phase to the first emulsifier aqueous solution is 1:2-20, and the volume ratio of the colostrum to the second emulsifier aqueous solution is 1:2-10.

7. The method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammation areas according to claim 1, characterized in that: The polycation is one or more of polyethyleneimine, chitosan, methacrylamide chitosan, gelatin and peptides, and the concentration of the polycation solution is 0.1-20 mg / mL.

8. The method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammation areas according to claim 1, characterized in that: In the monomer solution of the adhesion layer, the acrylic acid concentration is 0.1-0.8 mol / L, the molar ratio of AA to NHS is 1-30:1, the molar ratio of the photoinitiator to the monomer is 1:50-300, and the molar ratio of the crosslinking agent to the monomer is 1:50-300.

9. A polymer drug-loaded particle that targets and adheres to intestinal inflammation areas, characterized in that: The method is prepared by the method according to any one of claims 1 to 8.

10. The use of the polymer drug-loaded particles as claimed in claim 1, characterized in that: Used for preparing medicines for treating inflammatory bowel disease.

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