Polymer drug-loaded particles that target and adhere to intestinal inflammatory regions, their preparation methods and applications

Abstract

This invention discloses a polymer drug-loaded particle that targets and adheres to intestinal inflammatory regions, its preparation method, and its applications. The method involves first surface-modifying the biodegradable polymer drug-loaded particles with polycations, then adding these particles to a monomer solution for an adhesion layer. In situ polymerization on the particle surface is initiated by UV irradiation to form a PAN adhesion layer, resulting in polymer drug-loaded particles modified with this adhesion layer. The polycations serve as an intermediate layer, enabling successful modification of the PAN adhesion layer. The carboxyl groups in the adhesion layer give the particles a negative charge, while succinimide esters react with naturally occurring amino groups on the surface of inflamed intestinal tissue to form amide covalent bonds, ultimately achieving targeted adhesion to intestinal inflammatory sites. This adhesion strategy effectively applies PAN to micro / nano-scale drug-loaded particles to enhance their adhesion to damaged intestinal regions, providing a novel approach for the treatment of inflammatory bowel disease.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology and relates to a polymer drug-loaded particle, particularly to a polymer drug-loaded particle that targets and adheres to intestinal inflammatory regions, its preparation method, and its application. Background Technology

[0002] Most existing drugs for treating inflammatory bowel disease (IBD) are administered systemically, resulting in insufficient drug concentrations in the local intestinal damaged areas and numerous systemic side effects, such as neurotoxicity and nephrotoxicity. To improve drug concentrations in the local intestinal damaged areas, researchers have developed a series of drug delivery systems targeting these areas. Among them, biodegradable polymers such as polylactic-co-glycolic acid copolymer (PLGA) are widely used as biocompatible carrier materials for drug encapsulation and sustained release. However, due to their hydrophobicity and inertness, biodegradable polymer particles lack sufficient interaction with tissues, affecting drug retention and therapeutic efficacy 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.). Existing biodegradable polymer particles have limitations in the treatment of inflammatory bowel disease (IBD), particularly the lack of specific interaction between the particles and damaged intestinal tissue. While existing biodegradable polymer particles possess a certain degree of physical embedding and good biocompatibility, their hydrophobicity and bioinertness make it difficult to achieve stable tissue adhesion and drug retention in the complex intestinal environment. Therefore, an improved method is needed to enhance the interaction between biodegradable polymers and damaged intestinal tissue. Summary of the Invention

[0003] The purpose of this invention is to address the shortcomings of existing technologies by providing a polymer drug-loaded particle that targets and adheres to intestinal inflammatory regions, along with its preparation method and applications. This method involves surface modification of the degradable polymer drug-loaded particles to introduce covalent interactions, thereby enhancing the particles' adhesion to damaged intestinal tissue. Furthermore, by utilizing naturally occurring amino groups and other functional groups on the surface of inflamed intestinal tissue, an adhesion strategy capable of forming chemical bonds is designed to achieve targeted adhesion to intestinal inflammatory regions.

[0004] The technical solution adopted in this invention is as follows:

[0005] A method for preparing polymeric drug-loaded particles that target and adhere to intestinal inflammatory regions includes the following:

[0006] The desired drug loading and biodegradable polymer are dissolved in an organic solvent to form an organic phase. The organic phase is added to an aqueous solution of a first emulsifier and ultrasonically emulsified to form a primary emulsion. The primary emulsion is then added to an aqueous solution of a second emulsifier, stirred and evaporated overnight, centrifuged, washed, and freeze-dried to obtain biodegradable polymer drug-loaded particles.

[0007] Degradable polymer drug-loaded particles were added to a polycationic solution, stirred and incubated, then centrifuged, washed, and freeze-dried to obtain polymer particles with an intermediate layer modified.

[0008] The polymer particles modified with the intermediate layer were added to the monomer solution of the adhesion layer, which was a mixed solution containing AA acrylate and succinimide ester NHS, and a photoinitiator and crosslinking agent were added. In-situ polymerization was carried out by ultraviolet irradiation, followed by centrifugation, washing and freeze-drying to obtain the drug-loaded particles that target and adhere to the intestinal inflammatory region.

[0009] Furthermore, the biodegradable polymer is one or more selected from polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), polyglycolic acid (PGA), polycaprolactone (PCL), polyglycolic acid (PELA), and polyamino acids; furthermore, the organic solvent is one or more selected from dichloromethane, chloroform, benzene, toluene, ethyl acetate, and acetone.

[0010] Furthermore, the emulsifier is one or more of the following: Tween 20, Tween 80, PVA, polyoxyethylene (16) sorbitan monotall oleate, polyoxyethylene (10) sorbitan monolaurate, polyoxyethylene (20) sorbitan dioleate, polyoxyethylene (18) sorbitan monostearate, polyoxyethylene (3,8) glyceryl monolaurate, sodium oleate, sodium rosinate, C14-18 alkyl 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 to 20, and the volume ratio of the primary emulsion to the second emulsifier aqueous solution is 1:2 to 10.

[0013] Furthermore, the polycation is one or more selected from 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 the ratio is below this range, the resulting particles tend to agglomerate into white clumps, which is not conducive to subsequent processing and application. When the ratio is above this range, the final product has poor targeting effect, which is also not conducive to application. The molar ratio of photoinitiator to monomer is 1:50-300, and the molar ratio of crosslinking agent to monomer is 1:50-300.

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

[0016] This invention modifies the surface of drug-loaded biodegradable polymer particles with positively charged polycations via electrostatic adsorption. The polycation-modified polymer particles are then added to a monomer solution (acrylic acid, succinimidyl ester, or acrylate-N-succinimidyl ester, initiator, crosslinking agent, etc.) of the adhesion layer. UV irradiation initiates in-situ polymerization on the particle surface, forming a PAN (PAA-NHS, polyacrylate-N-hydroxysuccinimidyl ester) adhesion layer, resulting in polymer particles modified with the adhesion layer. The polycation serves as an intermediate layer, enabling successful modification of the PAN adhesion layer. The carboxyl groups in the adhesion layer give the particles a negative charge, allowing them to bind to the large number of positively charged proteins accumulated at inflamed sites. Simultaneously, succinimidyl ester (NHS) reacts with naturally occurring amino groups on the surface of inflamed intestinal tissue to form amide covalent bonds, ultimately achieving targeted adhesion to intestinal inflammation sites. This adhesion strategy effectively applies PAN to micro / nano-scale drug-loaded particles to enhance their adhesion to damaged intestinal areas, providing a novel approach for the treatment of inflammatory bowel disease.

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

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

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

[0020] (3) This invention effectively reduces side effects during drug delivery by introducing an adhesive coating on the surface of biodegradable polymer particles, ensuring the safety of drug application. No significant systemic toxicity was observed during treatment, 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 this invention has good biocompatibility and clinical application prospects. Attached Figure Description

[0021] Figure 1 The images shown are transmission electron microscope (TEM) images and laser confocal microscope (LCM) images of the 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 from Example 1, Comparative Example 1, and Comparative Example 2.

[0023] Figure 3 The image shows a comparison 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 PLGA@PAN particles obtained in Comparative Example 3.

[0025] Figure 5 The image shows a comparison of the intestinal tissue adhesion ability of PLGA@PEI@PAN(c,d) and PLGA(a,b) particles obtained from Example 1.

[0026] Figure 6 The bar chart shows the drug delivery and retention capabilities of the PLGA@PEI@PAN particles obtained in Example 1. Detailed Implementation

[0027] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0028] Example 1

[0029] Step 1: Preparation of PLGA drug-loaded particles: 15 mg tacrolimus and 400 mg PLGA were dissolved in 4 mL of dichloromethane to form an organic phase. This solution was slowly added to 20 mL of 1% polyvinyl alcohol (PVA) aqueous solution, and emulsified using an ultrasonic device (50 W, 10 seconds on, 3 seconds off) to form a pre-emulsion. Subsequently, the pre-emulsion was added to 60 mL of 0.5% PVA solution and stirred overnight for evaporation. Finally, the mixture was centrifuged (10000 rpm, 3 minutes) and washed at least 3 times, then lyophilized to obtain PLGA drug-loaded particles.

[0030] Step 2: Add PLGA particles to 40 mL of 0.5 mg / mL PEI solution and incubate with stirring for 4 hours. Centrifuge and wash three times, then freeze-dry to obtain PEI-modified PLGA particles (PLGA@PEI).

[0031] Step 3: Add PLGA@PEI particles to 5 mL of a mixed solution containing AA (150 μL, 2.2 mmol) and NHS (15 mg, 0.09 mmol), and simultaneously add photoinitiator I2959 (2.5 mg) and crosslinking agent N,N'-methylenebisacrylamide (3 mg). Expose the solution to UV light (365 nm, 120 mW / cm²). 2 Irradiation for 300 seconds initiates in-situ polymerization. After centrifugation and washing three times, the particles are lyophilized and stored to obtain PLGA particles modified with an adhesion layer (PLGA@PEI@PAN).

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

[0033] See results Figure 1 This indicates that PLGA@PEI@PAN has a core-shell structure, and the adhesion layer modified particles were successfully prepared.

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

[0035] See results Figure 2 This indicates that PLGA@PEI@PAN undergoes a surface charge transition from negative to positive to negative during preparation, corresponding to the charge properties of PLGA, PEI, and PAN. The results demonstrate that the intermediate layer can effectively achieve the charge transition from negative to positive on the PLGA particle surface, which is crucial for the in-situ polymerization of adsorbed negatively charged monomers.

[0036] To verify whether the adhesive layer modified particles contain NHS active groups and have reactivity with amino groups, infrared spectroscopy was performed on the particles: the PLGA@PEI@PAN prepared in Example 1 was compressed into tablets using potassium bromide and then subjected to infrared spectroscopy.

[0037] See results Figure 3The infrared spectrum shows that, compared with the PLGA particles without adhesive layer modification prepared in Comparative Example 1 (top image), the PLGA@PEI@PAN particles with adhesive layer modification prepared in Example 1 (bottom image) have a higher spectral density at 1367 cm⁻¹. -1 An enhanced infrared peak appeared at [location], corresponding to the tensile vibration peak of CN, which is also a characteristic peak of the NHS group. The results indicate that the adhesive layer modified particles contain NHS active groups and possess reactivity with amino groups.

[0038] Example 2

[0039] Step 1: Preparation of PLGA drug-loaded particles: 15 mg tacrolimus and 400 mg PLGA were dissolved in 4 mL of dichloromethane to form an organic phase. This solution was slowly added to 20 mL of 1% polyvinyl alcohol (PVA) aqueous solution, and emulsified using an ultrasonic device (50 W, 10 seconds on, 3 seconds off) to form a pre-emulsion. Subsequently, the pre-emulsion was added to 60 mL of 0.5% PVA solution and stirred overnight for evaporation. Finally, the mixture was centrifuged (10000 rpm, 3 minutes) and washed at least 3 times, then lyophilized to obtain PLGA drug-loaded particles.

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

[0041] Step 3: Add PLGA@CS particles to 5 mL of a mixed solution containing AA (150 μL, 2.2 mmol) and NHS (15 mg, 0.09 mmol), and simultaneously add photoinitiator I2959 (2.5 mg) and crosslinking agent N,N'-methylenebisacrylamide (3 mg). Expose the solution to UV light (365 nm, 120 mW / cm²). 2 Irradiation for 300 seconds initiates in-situ polymerization. After centrifugation and washing three times, the particles are freeze-dried and stored to obtain PLGA particles modified with an adhesion layer (PLGA@CS@PAN).

[0042] Comparative Example 1

[0043] Preparation of PLGA drug-loaded particles: 15 mg tacrolimus and 400 mg PLGA were dissolved in 4 mL of dichloromethane to form an organic phase. This solution was slowly added to 20 mL of 1% polyvinyl alcohol (PVA) aqueous solution, and emulsified using an ultrasonic device (50 W, 10 seconds on, 3 seconds off) to form a pre-emulsion. Subsequently, the pre-emulsion was added to 60 mL of 0.5% PVA solution and stirred for evaporation overnight. Finally, the mixture was centrifuged (10000 rpm, 3 minutes) and washed at least 3 times, then lyophilized to obtain PLGA drug-loaded particles.

[0044] Comparative Example 2

[0045] Step 1: Preparation of PLGA drug-loaded particles: 15 mg tacrolimus and 400 mg PLGA were dissolved in 4 mL of dichloromethane to form an organic phase. This solution was slowly added to 20 mL of 1% polyvinyl alcohol (PVA) aqueous solution, and emulsified using an ultrasonic device (50 W, 10 seconds on, 3 seconds off) to form a pre-emulsion. Subsequently, the pre-emulsion was added to 60 mL of 0.5% PVA solution and stirred overnight for evaporation. Finally, the mixture was centrifuged (10000 rpm, 3 minutes) and washed at least 3 times, then lyophilized to obtain PLGA drug-loaded particles.

[0046] Step 2: Add PLGA particles to 40 mL of 0.5 mg / mL PEI solution and incubate with stirring for 4 hours. Centrifuge and wash three times, then freeze-dry to obtain PEI-modified PLGA particles (PLGA@PEI).

[0047] Comparative Example 3

[0048] Step 1: Preparation of PLGA drug-loaded particles: 120 mg rapamycin and 400 mg PLGA were dissolved in 4 mL of dichloromethane to form an organic phase. This solution was added to 20 mL of 1% polyvinyl alcohol (PVA) aqueous solution and emulsified using an ultrasonic device (50 W ultrasonic power, 10 seconds on, 3 seconds off) to form a pre-emulsion. Subsequently, the pre-emulsion was added to 60 mL of 0.5% PVA solution and stirred for evaporation overnight. Finally, the mixture was centrifuged (10000 rpm, 3 minutes) and washed at least 3 times, then lyophilized to obtain PLGA drug-loaded particles.

[0049] Step 2: Prepare a reaction solution with an AA:NHS molar ratio of 4:1 and an acrylic acid monomer concentration of 0.49 mol / L: Add 200 μL of acrylic acid (2.92 mmol), 8 mg of I2959, and 9.4 mg of NN-methylenebisacrylamide to 5600 μL of water. Dissolve 123.5 mg of acrylate-N-succinimide ester (0.73 mmol) in 200 μL of N,N-dimethylformamide and then add it to the above mixture.

[0050] Step 3: Add PLGA particles to the above 6 mL mixture and ultrasonically disperse until homogeneous. Initiate polymerization by UV irradiation for 300 s to obtain particles (PLGA@PAN) that undergo in-situ UV photopolymerization without an intermediate layer. After polymerization, centrifuge and wash at least three times. Freeze-dry and store at low temperature.

[0051] Morphology testing 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 microscopy testing, in which the PAN adhesion layer was labeled with blue fluorescent dye 7-amino-4-methylcoumarin, and the PLGA particle core was labeled with red fluorescent dye Nile Red.

[0052] See results Figure 4 The results show that the PLGA@PAN particles are spherical with an indistinct core-shell structure, and no obvious PAN adhesion layer appears on the particle surface. This demonstrates the crucial role and necessity of the intermediate layer in the in-situ polymerization of the adhesion layer on the particle surface. The introduction of the intermediate layer allows it to adsorb onto the PLGA particles and effectively adsorb negatively charged monomers, resulting in a higher local monomer concentration on the particle surface, which is beneficial for in-situ polymerization of monomers on the particle surface.

[0053] Application Example 1

[0054] To investigate whether modification of the adhesion layer could improve adhesion to sites of intestinal inflammation, tissue adhesion tests were conducted on PLGA@PEI@PAN particles prepared in Example 1 and PLGA particles prepared in Comparative Example 1. To induce acute colitis, mice were given 2.0% sodium dextran sulfate (DSS) in drinking water for 7 days, followed by 5 days of normal drinking water for recovery. One day after DSS administration, mice were orally administered the same amount of PLGA or PLGA@PEI@PAN daily until they were euthanized. The colon, intestines, and other organs of the mice were removed for small animal in vivo imaging, with Nile Red labeling used for PLGA@PEI@PAN prepared in Example 1 and PLGA prepared in Comparative Example 1.

[0055] See results Figure 5 Live animal imaging images show that, compared to Figure 5 (a) PLGA particles prepared in Comparative Example 1 without the adhesion layer modification 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 investigate whether adhesion layer modified particles can improve drug retention, drug concentration tests were conducted on PLGA@PEI@PAN particles prepared in Example 1 and PLGA particles prepared in Comparative Example 1: drugs were loaded into PLGA@PEI@PAN and PLGA particles. To induce acute colitis, mice were given 2.0% sodium dextran sulfate (DSS) in drinking water for 7 days, followed by 5 days of normal drinking water for recovery. One day after DSS administration, mice received either drug-loaded PLGA or PLGA@PEI@PAN particles daily until they were sacrificed. The mouse colon was removed, cut into small pieces, weighed, and homogenized using a T18 ULTRA-TURRAX homogenizer (IKA Co., Ltd.) with 0.5 mL of physiological saline. 2 mL of acetonitrile was added to the homogenate, and the mixture was then vortexed in an ice bath for 30 minutes. After centrifugation at 4000 rpm for 15 minutes at 4 °C, the supernatant was dried and reconstituted in 100 μL of acetonitrile, and then stored at -20 °C until analysis by high-performance liquid chromatography-mass spectrometry (HPLC-MS).

[0058] See results Figure 6 Compared to direct administration of free drugs, the drug-loaded adhesive-modified particles PLGA@PEI@PAN exhibit higher drug concentrations in the intestine, indicating that the particles have good drug delivery performance, effectively improving drug utilization efficiency and reducing systemic side effects.

[0059] The embodiments described above are merely some preferred embodiments of the present invention, and are not intended to limit the invention. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the invention. Therefore, all technical solutions obtained by equivalent substitution or equivalent transformation fall within the protection scope of the present invention.

Claims

1. A method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammatory regions, characterized in that, include: The desired drug loading and the biodegradable polymer are dissolved in an organic solvent to form an organic phase. The organic phase is added to an aqueous solution of a first emulsifier and ultrasonically emulsified to form a primary emulsion. The primary emulsion is then added to an aqueous solution of a second emulsifier, stirred and evaporated overnight, centrifuged, washed, and freeze-dried to obtain biodegradable polymer-loaded particles. The biodegradable polymer is polylactic acid-glycolic acid copolymer (PLGA). Degradable polymer drug-loaded particles were added to a polycationic solution, stirred and incubated, then centrifuged, washed, and freeze-dried to obtain polymer particles with an intermediate layer modified; the polycationic solution was polyethyleneimine (PEI). The polymer particles modified with the intermediate layer were added to the monomer solution of the adhesion layer, which was a mixed solution containing AA acrylate and NHS succinimide ester, and a photoinitiator and crosslinking agent were added. In-situ polymerization was carried out by ultraviolet irradiation, followed by centrifugation, washing and freeze drying to obtain the polymer drug-loaded particles PLGA@PEI@PAN that target and adhere to the intestinal inflammation region, wherein PAN is polyacrylic acid-N-hydroxysuccinimide.

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

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

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

5. The method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammatory regions according to claim 1, characterized in that, The volume ratio of the organic phase to the aqueous solution of the first emulsifier is 1:2~20, and the volume ratio of the primary emulsion to the aqueous solution of the second emulsifier is 1:2~10.

6. The method for preparing polymer drug-loaded particles that target and adhere to intestinal inflammatory regions according to claim 1, characterized in that, The concentration of the polycationic solution is 0.1~20 mg / mL.

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

8. A polymeric drug-loaded particle that targets and adheres to intestinal inflammatory regions, characterized in that, It is prepared by the method described in any one of claims 1-7.

9. The application of the polymer drug-loaded particles as described in claim 8, characterized in that, Used to prepare drugs for the treatment of inflammatory bowel disease.

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