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CN-122005441-A - Hydrogel and preparation method and application thereof

CN122005441ACN 122005441 ACN122005441 ACN 122005441ACN-122005441-A

Abstract

The invention relates to a hydrogel, which comprises caffeic acid functionalized gelatin, polylysine and drug-loaded liposome. The hydrogels are capable of responding to oxidative stress environments, precisely controlling drug release, extending drug action time, and providing adequate physical strength and tissue adhesion.

Inventors

  • MENG FANHANG

Assignees

  • 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院）

Dates

Publication Date
20260512
Application Date
20260226

Claims (10)

  1. 1. A hydrogel comprising caffeic acid functionalized gelatin, polylysine, and drug loaded liposomes.
  2. 2. The hydrogel of claim 1, wherein the caffeic acid functionalized gelatin is prepared from gelatin, adipic acid dihydrazide, and caffeic acid.
  3. 3. The hydrogel of claim 1, wherein the drug-loaded liposomes are prepared from liposome-forming materials comprising soybean lecithin, cholesterol, and a nanocomposite consisting essentially of distearoyl phosphatidylethanolamine, a ketal, and polyethylene glycol, and wherein the drug comprises a PPAR alpha agonist.
  4. 4. A method for preparing a hydrogel according to claims 1-3, comprising the steps of: Preparing caffeic acid functionalized gelatin, namely respectively dissolving gelatin and adipic acid dihydrazide, mixing, reacting, dialyzing and purifying, freeze-drying to obtain gelatin-oxalic acid dihydrazide, dissolving gelatin-oxalic acid dihydrazide, activating, adding caffeic acid solution for reaction, dialyzing and purifying, and freeze-drying to obtain caffeic acid functionalized gelatin; the preparation of drug-loaded liposome comprises dissolving soybean lecithin, cholesterol and nanocomposite respectively, adding drug, rotary evaporating to obtain lipid membrane, adding solvent to hydrate lipid membrane, performing ultrasound on ice, filtering to obtain liposome emulsion suspension, centrifuging to remove free drug; the preparation method of the hydrogel comprises dissolving caffeic acid functionalized gelatin, adding polylysine and drug-loaded liposome solution, stirring and mixing in ice bath, and standing to obtain the hydrogel.
  5. 5. The preparation method of the caffeic acid functionalized gelatin according to claim 4, wherein the preparation method comprises the steps of dissolving gelatin in water, dissolving adipic acid dihydrazide in a buffer solution, mixing the two, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide for reaction, dialyzing and purifying by using a dialysis bag after the reaction is finished, freeze-drying to obtain gelatin-oxalic acid dihydrazide, dissolving gelatin-oxalic acid dihydrazide in the buffer solution, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide for light-shielding activation, adding a DMSO solution of caffeic acid for reaction, dialyzing and purifying by using a dialysis bag after the reaction is finished, and freeze-drying to obtain the caffeic acid functionalized gelatin.
  6. 6. The preparation method of the drug-loaded liposome according to claim 4, wherein the preparation method comprises the steps of dissolving soybean lecithin, cholesterol and nanocomposite materials in an organic solvent, adding a drug solution, rotationally evaporating the mixed solution to obtain a lipid membrane, adding a phosphate buffer solution to hydrate the lipid membrane, performing ultrasound on ice, filtering to obtain a liposome emulsion suspension, and centrifuging to remove free drugs.
  7. 7. The method of claim 6, wherein the method of preparing the drug-loaded liposome comprises membrane hydration, and the organic solvent comprises dichloromethane.
  8. 8. The method according to claim 4, wherein the preparation of the hydrogel comprises the steps of dissolving caffeic acid functionalized gelatin in a phosphate buffer solution, adding the phosphate buffer solution containing polylysine and drug-loaded liposome dropwise into the caffeic acid functionalized gelatin solution, stirring and mixing the mixture uniformly in an ice bath, and standing the mixture to obtain the hydrogel.
  9. 9. The method for producing a caffeic acid functionalized gelatin according to any one of claims 4 to 8, wherein the mass ratio of gelatin to adipic acid dihydrazide is (6 to 10) 1, and the mass ratio of gelatin-oxalic acid dihydrazide to caffeic acid is (0.1 to 0.5); In the preparation of the drug-loaded liposome, the mass ratio of soybean lecithin to cholesterol to nanocomposite is (10-30): 5-15): 0.5-2; in the preparation of the hydrogel, the mass ratio of the caffeic acid functional gelatin to the polylysine to the drug-loaded liposome is (150-450): (150-250): (0.1-2).
  10. 10. Use of a hydrogel according to claims 1-3, or a hydrogel obtained by the method of preparation according to claims 4-9, for the preparation of a product for the treatment of renal injury.

Description

Hydrogel and preparation method and application thereof Technical Field The invention relates to the technical field of hydrogels, in particular to a hydrogel and a preparation method and application thereof. Background Post-nephrectomy traumatic hemorrhage is a common and urgent complication in renal surgery that can not only lead to increased patient blood loss, but also affect the post-operative recovery process. In clinical treatment, although bleeding can be controlled to some extent by mechanical suturing, cauterization or topical hemostatic materials, these methods often fail to provide both hemostatic and tissue repair functions and may still cause further tissue damage after surgery. More seriously, in operations such as renal partial excision, temporary blockage of the renal arteries and even the renal veins is often required to reduce bleeding and facilitate handling, resulting in local or complete ischemia of the renal tissue. After blocking and releasing, the blood reperfusion can restore blood supply, but a series of pathological processes such as oxidative stress, inflammatory reaction, apoptosis, iron death and the like can be triggered, thereby triggering kidney Ischemia Reperfusion Injury (IRI) and further aggravating nephron injury and kidney function decline. Existing IRI treatments rely primarily on antioxidants, anti-inflammatory drugs, and drug delivery systems, but these methods generally only provide relief from some of the symptoms and fail to significantly reduce the damage caused by ischemia reperfusion. Even if the drug can reach the kidney through the delivery system, the problems of inaccurate release, low solubility and bioavailability and the like still exist, and the optimal curative effect is difficult to be exerted in a proper time and environment. In addition, although local administration can improve the drug concentration to a certain extent, the existing system lacks responsiveness to oxidative stress environment, has insufficient release pertinence and limited curative effect. Meanwhile, the existing partial injectable hydrogel has weak adhesion force at the operation site, insufficient mechanical property and strength, and is difficult to adapt to complex physiological environments in the processes of nephrectomy and ischemia reperfusion. The defects of the prior art are mainly characterized in that firstly, medicine solubility is poor, especially water-insoluble medicines are difficult to effectively transfer to a target area, quick and accurate medicine release cannot be achieved, secondly, the existing medicine delivery system lacks response to oxidative stress environments, so that the medicines cannot be released at the most appropriate time and cannot fully exert the therapeutic effect, thirdly, the local delivery system cannot always consider enough physical strength and tissue adhesiveness to influence the hemostatic and repairing effects while ensuring the medicine effect, and finally, the existing treatment method cannot meet requirements on both hemostatic and therapeutic aspects, so that kidney injury caused by IRI cannot be effectively relieved and tissue repair cannot be promoted. PPARα agonist Pemafibrate is a drug with remarkable anti-inflammatory, antioxidant and kidney function protecting effects, and can effectively reduce oxidative stress, inhibit inflammatory reaction, and improve kidney function recovery. However, pemafibrate is a water-insoluble drug, so that the bioavailability is low, the duration of the drug effect in vivo is short, and the effective drug concentration in the kidney injury area is difficult to maintain, so that the therapeutic effect is limited. Meanwhile, pemafibrate has limited transmission capacity through the kidney, and particularly in the kidney ischemia reperfusion process, drugs cannot be effectively targeted to damaged areas, so that the treatment effect is not ideal. In order to enhance the delivery of drugs, prior studies have often used a variety of carrier materials. However, conventional liposome systems, while capable of improving drug solubility and bioavailability, lack the ability to respond to specific physiological conditions (e.g., oxidative stress), resulting in inaccurate control of drug release timing and rate. In addition, although natural polymer materials such as chitosan and polylysine have good biocompatibility and degradability, the physical strength and the adhesiveness of the materials with tissues are insufficient in the treatment of kidney injury, so that the stability and the curative effect of the materials at an operation position are affected. The current drug delivery systems still have difficulty in achieving accurate drug release, prolonged action time, and effective targeting, resulting in a failure of the therapeutic effect to reach the desired level. Thus, the preparation of a multi-functional therapeutic system that responds to oxidative stress conditions, precisely controls drug