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CN-121987554-A - Drug delivery system for treating skin injury and preparation method and application thereof

CN121987554ACN 121987554 ACN121987554 ACN 121987554ACN-121987554-A

Abstract

The invention relates to a drug delivery system for treating skin injury, a preparation method and application thereof, wherein the delivery system comprises nanofibers formed by polylactic acid and multi-arm polyglycerol, and nano hydrogel loaded on the nanofibers, and the nano hydrogel raw material comprises bio-adhesion nano particles based on the polylactic acid-multi-arm polyglycerol and a polymer material containing amino groups. The drug delivery system provided by the invention has good humidity environment maintaining capability, mechanical strength and moderate fluidity, can improve the antibacterial property and stability of the material, and has a drug slow release effect.

Inventors

  • MAI YANG
  • Yuan Banghao
  • SUI YUSHENG
  • DOU LIU

Assignees

  • 深圳奥礼生物科技有限公司

Dates

Publication Date
20260508
Application Date
20260403

Claims (10)

  1. 1. A drug delivery system for treating skin lesions, comprising nanofibers formed from polylactic acid and multi-arm polyglycerol, and a nanohydrogel supported on the nanofibers; The nano hydrogel raw material comprises bio-adhesion nano particles based on polylactic acid-multi-arm polyglycerol and a polymer material containing amino groups.
  2. 2. The drug delivery system of claim 1, wherein the polymeric material comprises one or more of collagen, gelatin, chitosan, carboxymethyl chitosan, N-trimethyl chitosan, chitosan hydrochloride, or aminated hyaluronic acid; And/or the bioadhesive nanoparticles and the polymeric material form a hydrogel through a schiff base reaction; and/or the concentration ratio of the bioadhesive nano particles to the high polymer material is 1:0.01-20.
  3. 3. A pharmaceutical composition for treating skin lesions, characterized in that it comprises the drug delivery system of claim 1 or 2 and a therapeutic agent.
  4. 4. The pharmaceutical composition of claim 3, wherein the therapeutic agent is selected from one or more of a protein polypeptide drug, a nucleic acid drug, and a poorly soluble drug.
  5. 5. A method of preparing the pharmaceutical composition of claim 3 or 4, comprising: (1) Dissolving a polylactic acid-multi-arm polyglycerol polymer and a therapeutic agent in a first solvent to obtain a therapeutic agent @ NNPs; (2) Reacting the therapeutic agent @ NNPs prepared in step (1) with a sodium periodate solution to obtain a therapeutic agent @ BNPs; (3) Uniformly mixing the therapeutic agent @ BNPs prepared in the step (2) with a high polymer material containing amino groups, and reacting to obtain the nano hydrogel loaded with the therapeutic agent; (4) And (3) loading the nano hydrogel loaded with the therapeutic agent and prepared in the step (3) into nano fibers formed by polylactic acid and multi-arm polyglycerol to obtain the pharmaceutical composition.
  6. 6. The method of claim 5, wherein in step (2), the therapeutic agent @ NNPs is present at a concentration of 10-50 mg/mL; And/or in the step (2), the concentration of the sodium periodate solution is 0.05-0.5 mol/L; and/or in the step (2), the volume ratio of the sodium periodate solution to the therapeutic agent @ NNPs is 0.5-3:1.
  7. 7. The method of claim 5, wherein in step (3), the amino group-containing polymeric material comprises one or more of collagen, gelatin, chitosan, carboxymethyl chitosan, N-trimethyl chitosan, chitosan hydrochloride, or aminated hyaluronic acid; And/or the concentration ratio of the therapeutic agent @ BNPs to the high molecular material is 1:0.01-20; and/or, inverting every 5s for 3-8 min before uniformly mixing, and inverting every 10s after uniformly mixing.
  8. 8. The method of claim 5, wherein in step (1), the first solvent is selected from one or more of acetone, acetonitrile, benzyl alcohol, chloroform, methylene chloride, dioxane, dimethyl carbonate, DMSO, ethanol, ethyl acetate, ethyl formate, ethyl propionate, tetraethyl glycol ether, hexafluoroisopropanol, dimethyl isosorbide, isopropanol, methyl chloride, methyl ethyl ketone, N-methylpyrrolidone, propylene carbonate, and tetrahydrofuran; and/or, in the step (4), the nanofiber is prepared by adopting an electrostatic spinning process.
  9. 9. Use of the drug delivery system of claim 1 or 2 in the preparation of a delivery drug carrier.
  10. 10. Use of a pharmaceutical composition according to claim 3 or 4 for the manufacture of a medicament for the treatment of skin lesions.

Description

Drug delivery system for treating skin injury and preparation method and application thereof Technical Field The invention relates to the technical field of biological medicine, in particular to a drug delivery system for treating skin injury, and a preparation method and application thereof. Background Superficial burns are the most common type of skin injury in daily medical treatment, and although the surface symptoms are relatively mild, if improperly treated, problems such as infection, repeated inflammation, delayed healing, and scar formation are easily caused. The traditional burn dressing such as paraffin gauze and absorbent cotton has the defects that (1) the wound surface is easy to adhere and needs to be frequently replaced, secondary damage is easy to be caused, pain and treatment cost of a patient are increased, (2) mechanical support is insufficient, stable form of the wound surface cannot be maintained, tissue regeneration is affected, (3) the wet healing environment regulation and control capability is lacking, ideal conditions are difficult to be provided for cell migration and epithelialization, and (4) long-acting drug delivery is difficult to be realized by a single material, and the intervention on inflammation and scar formation is limited. In recent years, although electrospun nanofibers and hydrogel materials have been developed in wound surface management, it is still difficult for a single material to simultaneously meet the comprehensive requirements of adhesion, mechanical strength, gas permeability, wet healing, drug release and the like. In addition, androgens and their receptors (ARs) play a negative regulatory role in wound inflammation and healing, but existing AR inhibitors have drug resistance, limited therapeutic effects, and lack of carriers available for topical long-term administration to wounds. Therefore, there is an urgent need in the art for a new composite material that combines bioadhesion, mechanical support, controlled drug release, and adaptation to biomacromolecule therapeutics (e.g., PROTAC drugs) to meet the clinical demands of dressing performance and new mechanism drug co-therapy in superficial burn treatment. Disclosure of Invention In order to overcome the defects in the prior art, the invention provides a three-dimensional (3D) composite biomedical delivery system which is based on gel formed by Bioadhesive Nano Particles (BNPs) and a high polymer material and then is constructed in cooperation with electrospun fibers formed by polylactic acid-multi-arm polyglycerol (PLA-HPG). Specifically, BNPs is composed of PLA-HPG polymer material, the surface is modified to be rich in aldehyde groups which can form Schiff base with amino groups, so that the modified surface can form a dynamic covalent cross-linked three-dimensional porous reticular hydrogel structure with amino-rich high polymer material (such as carboxymethyl chitosan), further, the three-dimensional porous reticular hydrogel is integrated with fibers prepared by an electrostatic spinning process in a covalent way, so that the modified three-dimensional porous reticular hydrogel has good humidity environment maintenance capability, mechanical strength and moderate fluidity, and can improve the antibacterial property and stability of the material, further, the composite material can load medicines (such as PROTAC medicines), long-acting slow release of the medicines can be realized, the stability can be kept on a wound surface, and the replacement frequency can be reduced. In order to achieve the above purpose, the present invention adopts the following technical scheme: The invention provides a drug delivery system for treating skin injury, which comprises nanofibers formed by polylactic acid and multi-arm polyglycerol, and nano hydrogel loaded on the nanofibers; The nano hydrogel raw material comprises bio-adhesion nano particles based on polylactic acid-multi-arm polyglycerol and a polymer material containing amino groups. Preferably, the polymer material comprises one or more of collagen, gelatin, chitosan, carboxymethyl chitosan, N-trimethyl chitosan, chitosan hydrochloride or amino hyaluronic acid. Preferably, the bioadhesive nanoparticles and the polymeric material form a hydrogel by a schiff base reaction. Preferably, the concentration ratio of the bioadhesive nano particles to the high polymer material is 1:0.01-20. The invention provides a pharmaceutical composition for treating skin injury, which comprises the drug delivery system and a therapeutic agent. Preferably, the therapeutic agent is selected from one or more of a protein polypeptide drug, a nucleic acid drug, and a poorly soluble drug. The invention provides a method for preparing the pharmaceutical composition, which comprises the following steps: (1) Dissolving a polylactic acid-multi-arm polyglycerol polymer and a therapeutic agent in a first solvent to obtain a therapeutic agent @ NNPs; (2) Reacting the therapeutic agent @