Inflammation response type drug-loaded microgel system with slow release characteristic

Abstract

The invention relates to the technical field of medicines, and discloses an inflammation response type drug-loaded microgel system with a slow release characteristic. A construction method of an inflammation response type drug-loaded microgel system with a slow release characteristic comprises the following steps: taking a solvent I dissolved with active drug components and carrier micromolecules as an oil phase, taking an aqueous solution II containing an emulsifier as a water phase, and mixing the oil phase and the water phase to form oil-in-water type emulsion droplets; after the oil-in-water type emulsion droplets are generated, removing the organic solvent in the emulsion droplets to realize droplet shrinkage, and in the droplet shrinkage process, self-assembling the carrier micromolecules and the active pharmaceutical ingredients to form the drug-loaded gel microspheres. According to the inflammation response type drug-loaded microgel system with the slow release characteristic, active drug components are effectively packaged in nanofibers, the active drug components are prevented from leaking in advance, the stability and bioavailability of drugs are improved, and meanwhile, the drug-loaded microgel microspheres have an enzyme response release mechanism and can be released according to needs, and the residence time is prolonged.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to an inflammation-responsive drug-loaded microgel system with sustained-release properties. Background Art

[0002] Local drug delivery injections, such as intra-articular injections, intravitreal injections, and middle ear injections, can improve drug bioavailability while reducing drug systemic toxicity. However, this method of drug delivery faces a major challenge: the drug is quickly cleared after injection, limiting its therapeutic effect. To address this problem, scientists have developed a variety of local drug delivery systems, including liposomes, micelles, polymer micro / nanoparticles, and hydrogels. These drug delivery systems were originally designed to extend the half-life and release time of the drug, but they each have their own advantages and disadvantages.

[0003] Although these local drug delivery systems have made some progress in extending the half-life of drugs and improving drug release characteristics, they still have some common problems. The most significant problem is that these systems usually experience an initial rapid release (burst release) followed by a slow sustained release phase. This release pattern may lead to excessively high initial drug concentrations, resulting in serious adverse reactions such as local irritation, inflammation, or systemic toxicity. In the subsequent release phase, the drug concentration drops rapidly and may not be able to maintain an effective therapeutic concentration, affecting the therapeutic effect.

[0004] An ideal topical drug delivery system should have the following characteristics: 1) Bioresponsiveness: Ability to adjust drug release according to specific stimuli in the body (such as pH, temperature, enzyme concentration, etc.) to ensure that the drug is released at an effective therapeutic concentration when needed.

[0005] 2) Release on demand: The release rate and amount of the drug can be adjusted according to the severity of the disease and the individual differences of the patients to achieve the best therapeutic effect.

[0006] 3) Prolong the retention time: It can reduce unnecessary drug release during the disease remission period, thereby prolonging the local retention time of the drug and improving the sustained treatment effect.

[0007] 4) High stability and biocompatibility: The drug delivery system should have high physicochemical stability and good biocompatibility to avoid causing adverse reactions or toxicity in the body.

[0008] In recent years, amphiphilic small molecule materials have become one of the hot topics of research due to their unique self-assembly ability and good biocompatibility. These materials can self-assemble to form nanofibers or microgel structures under specific conditions, effectively encapsulate drug molecules, and release drugs under biological stimulation, showing excellent sustained-release properties and inflammatory response capabilities. Therefore, in order to solve the above technical problems, the present invention provides an inflammatory-responsive drug-loaded microgel system with sustained-release properties. Summary of the invention

[0009] The purpose of the present invention is to provide an inflammatory responsive drug-loaded microgel system with sustained-release properties, which effectively encapsulates active drug ingredients in nanofibers to prevent their premature leakage, improve the stability and bioavailability of the drug, and at the same time, the drug-loaded gel microspheres have an enzyme-responsive release mechanism, which can be released on demand and prolong the retention time.

[0010] To achieve the above object, the present invention provides a method for constructing an inflammatory response drug-loaded microgel system with sustained release characteristics, comprising the following steps: Step 1, emulsification: Solvent I containing active pharmaceutical ingredients and carrier small molecules is used as the oil phase, and aqueous solution II containing an emulsifier is used as the water phase, and the two are mixed to form oil-in-water emulsion droplets; Step 2, self-assembly: After the oil-in-water emulsion droplets are generated, the organic solvent in the emulsion droplets is removed to achieve droplet shrinkage. During the droplet shrinkage process, the carrier small molecules and the active drug ingredients self-assemble to form drug-loaded gel microspheres.

[0011] Furthermore, in step 1, the volume ratio of the water phase to the oil phase is 1:2-20.

[0012] Furthermore, the emulsification method in step 1 includes one or more of ultrasound, mechanical stirring, high-pressure homogenization, membrane emulsification, and continuous flow; the method for removing the organic solvent in the emulsion droplets in step 2 includes one or more of continuous flow, rotary evaporation, and electrostatic spraying.

[0013] Furthermore, in step 1, the active pharmaceutical ingredient is a fatty acid-modified prodrug, and the carrier small molecule is an amphiphilic small molecule gel.

[0014] Further, the fatty acid prodrug structure is A-ester bond-B; wherein A includes tacrolimus, cyclosporin A, sirolimus, everolimus, azathioprine, leflunomide, mycophenolic acid, mycophenolate mofetil, dexamethasone, prednisone, prednisolone, methylprednisolone, hydrocortisone, cortisone, fludrocortisone, betamethasone, triamcinolone acetonide, triamcinolone acetonide, flunisolide, beclomethasone, fluticasone, mometasone, flumethasone, isoflurane, corticosterone, deoxycorticosterone acetate, deoxycorticosterone enanthate, 11-deoxycorticosterone, 11-deoxycorticosterone, aldosterone, budesonide, docetaxel, methotrexate, etoposide, fulvestrant, paricalcitol, teniposide, Paclitaxel, valrubicin, lamivudine, zidovudine, abacavir, emtricitabine, atazanavir, cobicistat, elvitegravir, ribavirin, albendazole, baclofen, benznidazole, nifurtimox, mefloquine, sulfadoxine, pyrimethamine, proguanil, amprenavir, amphotericin B, bexarotene, calcitriol, digoxin, doxorcalciferol, dronabinol, propofol, 6-mercaptopurine, 1-thyroxine, glyburide, parthenolide, tauroursodeoxycholic acid, ruxolitinib, tofacitinib, lisinopril, amlodipine, lidocaine, paliperidone, clarithromycin, clindamycin hydrochloride, fluconazole, rapamycin, perindopril, liraglutide, or a mixture of any of the following; B includes palmitic acid, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, stearic acid, oleic acid, palmitoleic acid, linoleic acid, α-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid or a mixture of one or more thereof. Further, the amphiphilic small molecule gelling agent includes a mixture of one or more thereof including ascorbyl palmitate, ascorbyl caprate, ascorbyl laurate, caprylic ascorbate, myristic acid ascorbate, oleic acid ascorbate, sorbitan monostearate, sorbitan caprate, sorbitol ester laurate, sorbitol fatty caprylate, myristic acid sorbitan ester, monopalmitic acid triglyceride, monolauric acid triglyceride, monocaprylic acid triglyceride, sucrose palmitate, sucrose caprate, sucrose laurate, sucrose caprylate, sucrose myristate and sucrose oleate.

[0015] Furthermore, in step 1, solvent I comprises one or a mixture of benzene, n-butanol, carbon tetrachloride, chloroform, cyclohexane, cyclopentane, dichloromethane, dichloroethane, ethyl acetate, ether, n-heptane, n-hexane, methyl ethyl ketone, isooctane, pentane, dipropyl ether, tetrachloroethane, toluene, trichloroethane, xylene or dimethyl carbonate.

[0016] Furthermore, in step 1, the emulsifier comprises one or a mixture of oleic acid soap, stearic acid soap, lauric acid soap, rosin oil soap, alkyl sulfate, alkylbenzene sulfonate, alkyl sulfonate, alkyl naphthyl sulfonate, lignin sulfonate, phosphate ester salt, sulfate ester salt, quaternary ammonium salt, alkyl ammonium salt, lecithin, fatty acid glyceride, polyvinyl alcohol, sucrose fatty acid ester, fatty acid sorbitan, polysorbate, polyoxyethylene fatty acid ester, polyoxyethylene fatty alcohol ether, polyoxyethylene-polyoxypropylene block copolymer, fluorocarbon surfactant, silicon-containing surfactant, biosurfactant, crown ether surfactant, gum arabic, tragacanth gum, gelatin, apricot gum, egg yolk, polyvinyl pyrrolidone or solid particulate emulsifier.

[0017] The present invention also provides an inflammatory response drug-loaded microgel system with sustained release characteristics. According to the above-mentioned construction method, the inflammatory response drug-loaded microgel system is a drug-loaded gel microsphere, the particle size of the drug-loaded gel microsphere is 1μm-500μm, the effective components of the drug-loaded gel microsphere include active drug ingredients and carrier small molecules for controlling drug release, the mass of the active drug ingredients accounts for 5-50% of the drug-loaded gel microsphere, and the encapsulation rate of the active drug ingredients is 5-100%.

[0018] The present invention also provides the use of the above-mentioned inflammation-responsive drug-loaded microgel system with sustained-release properties in constructing a drug delivery platform.

[0019] The advantages and positive effects of the inflammatory response drug-loaded microgel system with sustained release characteristics described in the present invention are: 1. The present invention uses amphiphilic small molecules as carrier materials, and the amphiphilic small molecules self-assemble to form nanofibers through hydrophilic-hydrophobic interactions, hydrogen bonds and π-π conjugation. During the self-assembly process, the fatty acid-modified prodrug molecules are effectively encapsulated in the nanofiber structure to prevent the active drug molecules from leaking in advance. This structure can effectively protect the drug molecules and improve the stability and bioavailability of the drug.

[0020] 2. The drug-loaded gel microspheres in the present invention have an enzyme-responsive release mechanism. The amphiphilic small molecule gel contains cleavable chemical bonds (such as ester bonds), which are cleaved under the action of enzymes in the body (such as esterases, matrix metalloproteinases, etc.) to release active drug ingredients. The release rate of active drugs is related to the concentration of the enzyme. Injecting or implanting drug-loaded microgels with sustained-release properties into joints can achieve long-term release of active drugs. The severity of arthritis affects the concentration of enzymes in the joints. When the joints are inflamed and enzymes are released, the enzymes decompose the microgel particles, thereby releasing anti-inflammatory drugs. After the anti-inflammatory drug is released, the enzyme concentration decreases, and the uncleaved microgels remain stable before the next inflammatory stimulus, thereby achieving on-demand release of drugs. Drug-loaded microgels can be used for the release of therapeutic agents for tissue regeneration at different stages, and are suitable for joint cavity, inner ear, eye and oral drug delivery.

[0021] 3. The inflammatory response drug-loaded microgel system of the present invention achieves efficient drug delivery and controlled release through advanced material design and microgel preparation process, and has important application prospects and broad market demand. Its inflammatory response characteristics and sustained release effect make it have important clinical value in the treatment of chronic diseases (such as arthritis, eye inflammation, inner ear diseases and tumors). In addition, the system can also be used in the field of tissue regeneration to promote tissue repair and regeneration by releasing the therapeutic agents required at different stages.

[0022] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a diagram of the self-assembly mechanism of carrier molecules and drug molecules in an embodiment of the present invention; Figure 2 This is an optical microscope photo of the microgel prepared in Example 1 of the present invention; Figure 3 The drug release curve of the microgel prepared in Example 1 of the present invention in PBS solution and 100 U / mL lipase; Figure 4 Drug release curves of the microgel prepared in Example 1 of the present invention in 200 U / mL lipase and under conditions of varying lipase concentrations. DETAILED DESCRIPTION

[0024] The technical solution of the present invention is further described below through the accompanying drawings and embodiments.

[0025] Unless otherwise defined, technical or scientific terms used in the present invention shall have the common meanings understood by one having ordinary skills in the field to which the present invention belongs.

[0026] Unless otherwise defined, the instruments, equipment and reagents used in the present invention are conventionally commercially available.

[0027] A method for constructing an inflammation-responsive drug-loaded microgel system with sustained-release properties comprises the following steps: Step 1, emulsification: Solvent I containing active pharmaceutical ingredients and carrier small molecules is used as the oil phase, and aqueous solution II containing emulsifier is used as the water phase, and the two are mixed to form water-in-oil emulsion droplets.

[0028] The volume ratio of the water phase to the oil phase is 1:2-20, and the emulsification method includes one or more of ultrasound, mechanical stirring, high-pressure homogenization, membrane emulsification, and continuous flow.

[0029] The active pharmaceutical ingredient is a fatty acid prodrug, and its structure is A-ester bond-B, A includes tacrolimus, cyclosporine A, sirolimus, everolimus, azathioprine, leflunomide, mycophenolic acid, mycophenolate mofetil, dexamethasone, prednisone, prednisolone, methylprednisolone, hydrocortisone, cortisone, fludrocortisone, betamethasone, triamcinolone acetonide, triamcinolone acetonide, flunisolide, beclomethasone, fluticasone, mometasone, flumethasone, isoflurane, corticosterone, deoxycorticosterone acetate, deoxycorticosterone enanthate, 11-deoxycorticosterone, 11-deoxycorticosterone, aldosterone, budesonide, docetaxel, methotrexate, etoposide, fulvestrant, paricalcitol, teniposide, paclitaxel, valrubicin, laproside Mivudine, zidovudine, abacavir, emtricitabine, atazanavir, cobicistat, elvitegravir, ribavirin, albendazole, baclofen, benznidazole, nifurtimox, mefloquine, sulfadoxine, pyrimethamine, proguanil, amprenavir, amphotericin B, bexarotene, calcitriol, digoxin, doxorcalciferol, dronabinol, propofol, 6-mercaptopurine, 1-thyroxine, glibenclamide, parthenolide, tauroursodeoxycholic acid, ruxolitinib, tofacitinib, lisinopril, amlodipine, lidocaine, paliperidone, clarithromycin, clindamycin hydrochloride, fluconazole, rapamycin, perindopril, liraglutide, or a mixture of any of the following:

[0030] B includes one or a mixture of palmitic acid, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, stearic acid, oleic acid, palmitoleic acid, linoleic acid, α-linolenic acid, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid.

[0031] The carrier small molecule is an amphiphilic small molecule gelling agent, and the amphiphilic small molecule gelling agent includes one or a mixture of ascorbyl palmitate, ascorbyl caprate, ascorbyl laurate, ascorbyl caprylate, myristic acid ascorbyl ester, oleic acid ascorbyl ester, sorbitan monostearate, sorbitan caprate, sorbitan laurate, sorbitan caprylate, myristic acid sorbitan ester, monopalmitic acid triglyceride, monolauric acid triglyceride, monocaprylic acid triglyceride, sucrose palmitate, sucrose caprate, sucrose laurate, sucrose caprylate, sucrose myristate and sucrose oleate.

[0032] Solvent I includes one or a mixture of benzene, n-butanol, carbon tetrachloride, chloroform, cyclohexane, cyclopentane, dichloromethane, dichloroethane, ethyl acetate, ethyl ether, n-heptane, n-hexane, methyl ethyl ketone, isooctane, pentane, dipropyl ether, tetrachloroethane, toluene, trichloroethane, xylene or dimethyl carbonate.

[0033] Emulsifiers include oleic acid soap, stearic acid soap, lauric acid soap, rosin oil soap, alkyl sulfates, alkylbenzene sulfonates, alkyl sulfonates, alkyl naphthyl sulfonates, lignin sulfonates, phosphate esters, sulfate esters, quaternary ammonium salts, alkyl ammonium salts, lecithin, fatty acid glycerides, polyvinyl alcohol, sucrose fatty acid esters, fatty acid sorbitan, polysorbate, polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, polyoxyethylene-polyoxypropylene block copolymers, fluorocarbon surfactants, silicon-containing surfactants, biosurfactants, crown ether surfactants, gum arabic, tragacanth gum, gelatin, apricot gum, egg yolk, polyvinyl pyrrolidone or a mixture of one or more of solid particulate emulsifiers.

[0034] Step 2, self-assembly: After the oil-in-water emulsion droplets are generated, the organic solvent in the emulsion droplets is removed to achieve droplet shrinkage. During the droplet shrinkage process, the carrier small molecules and the active drug ingredients self-assemble to form drug-loaded gel microspheres. The self-assembly mechanism of carrier molecules and drug molecules is as follows Figure 1 shown.

[0035] Methods for removing organic solvent from emulsion droplets include one or more of continuous flow, rotary evaporation, and electrostatic spray.

[0036] The inflammatory responsive drug-loaded microgel system obtained by the construction method is a drug-loaded gel microsphere, the particle size of the drug-loaded gel microsphere is 1μm-500μm, the effective components of the drug-loaded gel microsphere include active drug ingredients and carrier small molecules for controlling drug release, the mass of the active drug ingredients accounts for 5-50% of the drug-loaded gel microsphere, and the encapsulation rate of the active drug ingredients is 5-100%.

[0037] The following is a specific description with reference to embodiments.

[0038] Example 1: Dissolve triamcinolone acetonide palmitate (10 mg / mL) and ascorbyl palmitate (10 mg / mL) in ethyl acetate as the oil phase. Prepare an aqueous solution containing 1% polyoxyethylene-polyoxypropylene block copolymer as the water phase. Use a syringe pump to pass the two phases into a continuous flow device for emulsification to form an O / W emulsion. The organic solvent in the emulsion is quickly removed in the pipeline filled with 1% polyoxyethylene-polyoxypropylene block copolymer aqueous solution, and the droplets solidify into microspheres. Use a beaker to collect the microspheres, wash with ultrapure water, and dry them. Compared with traditional stirring or ultrasonic emulsification methods, continuous flow can provide more stable and gentle energy input, allowing the drug molecules and carrier molecules in the droplets to self-assemble in a more stable environment, which is beneficial to improving the stability of the system. The drug loading of the prepared microspheres is 45.51% and the encapsulation efficiency is 91.02%. The optical microscope photo of the microspheres is shown in the figure. Figure 2 shown.

[0039] Example 2: Budesonide palmitate (10 mg / mL) and ascorbyl palmitate (10 mg / mL) were dissolved in chloroform as the oil phase. An aqueous solution containing 1% polyoxyethylene-polyoxypropylene block copolymer was prepared as the aqueous phase. The two phases were emulsified into an O / W emulsion by a syringe pump through a continuous flow device. The organic solvent in the emulsion was quickly removed in a pipeline filled with 1% polyoxyethylene-polyoxypropylene block copolymer aqueous solution, and the emulsion droplets solidified into microspheres. The microspheres were received in a beaker, washed with ultrapure water, and dried to obtain the microspheres. The drug loading of the prepared microspheres was 41.67% and the encapsulation efficiency was 83.34%.

[0040] The microspheres prepared in Example 1 were subjected to drug release assay: Figure 3 The drug release curves of ascorbyl palmitate microspheres containing triamcinolone acetonide palmitate prepared under the conditions of Example 1 in PBS solution and 100 U / mL lipase are shown. The results show that the prepared microspheres have good stability under PBS physiological conditions, and show slow release in the presence of 100 U / mL lipase.

[0041] Figure 4 The drug release curves of ascorbyl palmitate microspheres containing triamcinolone acetonide palmitate prepared under the conditions of Example 1 in 200U / mL lipase and under conditions of varying lipase concentrations (day 5) are shown. The results show that the prepared microspheres show responsive release to the severity of the disease. Under conditions of simulating the acute phase of inflammation, i.e., a higher concentration of lipase, the drug release rate is accelerated. In the intermittent period of inflammation after the acute phase, the drug release rate slows down. This shows that the drug-loaded gel microspheres in the present invention have an enzyme-responsive release mechanism, can be released on demand, and prolong the retention time.

[0042] Therefore, the present invention adopts the above-mentioned inflammatory responsive drug-loaded microgel system with sustained-release characteristics to effectively encapsulate the active drug ingredients in nanofibers to prevent their premature leakage, improve the stability and bioavailability of the drug, and at the same time, the drug-loaded gel microspheres have an enzyme-responsive release mechanism, which can be released on demand and prolong the retention time.

[0043] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solution of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solution to deviate from the spirit and scope of the technical solution of the present invention.

Claims

1. A method for constructing an inflammatory response drug-loaded microgel system with sustained release characteristics, characterized in that: The following steps are involved: Step 1, emulsification: Solvent I containing active pharmaceutical ingredients and carrier small molecules is used as the oil phase, and aqueous solution II containing an emulsifier is used as the water phase, and the two are mixed to form oil-in-water emulsion droplets; Step 2, self-assembly: After the oil-in-water emulsion droplets are generated, the organic solvent in the emulsion droplets is removed to achieve droplet shrinkage. During the droplet shrinkage process, the carrier small molecules and the active drug ingredients self-assemble to form drug-loaded gel microspheres.

2. The construction method according to claim 1, characterized in that: The volume ratio of the water phase to the oil phase in step 1 is 1:2-20.

3. The construction method according to claim 1, characterized in that: The emulsification method in step 1 includes one or more of ultrasound, mechanical stirring, high-pressure homogenization, membrane emulsification, and continuous flow; the method for removing the organic solvent in the emulsion droplets in step 2 includes one or more of continuous flow, rotary evaporation, and electrostatic spraying.

4. The construction method according to claim 1, characterized in that: In step 1, the active pharmaceutical ingredient is a fatty acid-modified prodrug, and the carrier small molecule is an amphiphilic small molecule gel.

5. The construction method according to claim 4, characterized in that: The fatty acid prodrug structure is A-ester bond-B; wherein A includes tacrolimus, cyclosporin A, sirolimus, everolimus, azathioprine, leflunomide, mycophenolic acid, mycophenolate mofetil, dexamethasone, prednisone, prednisolone, methylprednisolone, hydrocortisone, cortisone, fludrocortisone, betamethasone, triamcinolone acetonide, triamcinolone acetonide, flunisolide, beclomethasone, fluticasone, mometasone, flumethasone, isoflurane, corticosterone, deoxycorticosterone acetate, deoxycorticosterone enanthate, 11-deoxycorticosterone, 11-deoxycorticosterone, aldosterone, budesonide, docetaxel, methotrexate, etoposide, fulvestrant, paricalcitol, teniposide, taxane Alcohol, valrubicin, lamivudine, zidovudine, abacavir, emtricitabine, atazanavir, cobicistat, elvitegravir, ribavirin, albendazole, baclofen, benznidazole, nifurtimox, mefloquine, sulfadoxine, pyrimethamine, proguanil, amprenavir, amphotericin B, bexarotene, calcitriol, digoxin, doxorcalciferol, dronabinol, propofol, 6-mercaptopurine, 1-thyroxine, glyburide, parthenolide, tauroursodeoxycholic acid, ruxolitinib, tofacitinib, lisinopril, amlodipine, lidocaine, paliperidone, clarithromycin, clindamycin hydrochloride, fluconazole, rapamycin, perindopril, liraglutide or a mixture of one or more thereof; B includes one or a mixture of palmitic acid, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, stearic acid, oleic acid, palmitoleic acid, linoleic acid, α-linolenic acid, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid.

6. The construction method according to claim 4, characterized in that: The amphiphilic small molecule gelling agent includes one or a mixture of ascorbyl palmitate, ascorbyl caprate, ascorbyl laurate, caprylic ascorbyl ester, myristic ascorbyl ester, oleic ascorbyl ester, sorbitan monostearate, sorbitan caprate, sorbitan laurate, sorbitan caprylate, myristic acid sorbitan ester, monopalmitic acid triglyceride, monolauric acid triglyceride, monocaprylic acid triglyceride, sucrose palmitate, sucrose caprate, sucrose laurate, sucrose caprylate, sucrose myristate and sucrose oleate.

7. The construction method according to claim 1, characterized in that: In step 1, the solvent I comprises one or a mixture of benzene, n-butanol, carbon tetrachloride, chloroform, cyclohexane, cyclopentane, dichloromethane, dichloroethane, ethyl acetate, ether, n-heptane, n-hexane, methyl ethyl ketone, isooctane, pentane, dipropyl ether, tetrachloroethane, toluene, trichloroethane, xylene or dimethyl carbonate.

8. The construction method according to claim 1, characterized in that: In step 1, the emulsifier comprises one or a mixture of oleic acid soap, stearic acid soap, lauric acid soap, rosin oil soap, alkyl sulfate, alkylbenzene sulfonate, alkyl sulfonate, alkyl naphthyl sulfonate, lignin sulfonate, phosphate ester salt, sulfate ester salt, quaternary ammonium salt, alkyl ammonium salt, lecithin, fatty acid glyceride, polyvinyl alcohol, sucrose fatty acid ester, fatty acid sorbitan, polysorbate, polyoxyethylene fatty acid ester, polyoxyethylene fatty alcohol ether, polyoxyethylene-polyoxypropylene block copolymer, fluorocarbon surfactant, silicon-containing surfactant, biosurfactant, crown ether surfactant, gum arabic, tragacanth gum, gelatin, apricot gum, egg yolk, polyvinyl pyrrolidone or solid particulate emulsifier.

9. An inflammatory response drug-loaded microgel system with sustained release characteristics, characterized in that: According to the construction method according to any one of claims 1 to 8, the inflammatory responsive drug-loaded microgel system is a drug-loaded gel microsphere, the particle size of the drug-loaded gel microsphere is 1 μm-500 μm, the effective components of the drug-loaded gel microsphere include active drug ingredients and carrier small molecules for controlling drug release, the mass of the active drug ingredients accounts for 5-50% of the drug-loaded gel microspheres, and the encapsulation efficiency of the active drug ingredients is 5-100%.

10. Use of the inflammatory responsive drug-loaded microgel system with sustained release properties as claimed in claim 9 in constructing a drug delivery platform.

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