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CN-121976387-A - Polyvinylpyrrolidone grafted polymethyl methacrylate diethylaminoethyl esterification chitosan nanofiber and preparation method and application thereof

CN121976387ACN 121976387 ACN121976387 ACN 121976387ACN-121976387-A

Abstract

The invention discloses a polyvinylpyrrolidone grafted polymethyl methacrylate diethylaminoethyl esterification chitosan nanofiber, a preparation method and application thereof. The invention discloses a method for preparing a porous nanofiber by modifying PVP and PDMAEMA on chitosan through an atom transfer radical polymerization method, dissolving the modified PVP and PDMAEMA in an acetic acid solution, carrying out high-voltage electrostatic spinning, completely soaking the obtained nanofiber in a foaming solution, washing the foamed nanofiber after stabilizing, carrying out air-release foaming treatment, freezing and freeze-drying to obtain the porous nanofiber, dissolving musk ketone in absolute ethyl alcohol, soaking the porous nanofiber in the musk ketone solution, and completely volatilizing the absolute ethyl alcohol. The invention provides an intelligent nanofiber dressing capable of actively sensing and responding to the change (pH) of the microenvironment of a diabetes wound. The dressing can realize the release of medicines as required, cooperatively manage wound exudates, remarkably improve blood circulation and antibacterial effect and promote the healing of diabetic wounds.

Inventors

  • LI FANGZHOU
  • ZHENG XIANG
  • LI MINGMEI
  • GAO PENGLI

Assignees

  • 中国医学科学院生物医学工程研究所

Dates

Publication Date
20260505
Application Date
20260206

Claims (10)

  1. 1. The preparation method of the polyvinylpyrrolidone grafted polymethyl methacrylate chitosan nanofiber is characterized by comprising the following steps of: s1, synthesizing polyvinylpyrrolidone grafted polymethyl methacrylate ethyl esterification chitosan: a. polymerizing a dimethylaminoethyl methacrylate monomer by using an atom transfer radical polymerization method and using brominated chitosan as a macromolecular initiator under a CuBr/PMDETA catalytic system and using 2, 2-bipyridine as a ligand to obtain chitosan grafted dimethylaminoethyl methacrylate; b. Through click chemistry, dissolving chitosan grafted poly (dimethylaminoethyl methacrylate) and polyvinylpyrrolidone polymer with a mercapto group at the end group in Trs-HCl buffer solution with the pH of 8.0, and carrying out continuous magnetic stirring reaction for 24-48 hours at 20-30 ℃ under the protection of nitrogen to obtain polyvinylpyrrolidone grafted poly (dimethylaminoethyl methacrylate) chitosan; S2, preparing electrostatic spinning nanofiber: dissolving polyvinylpyrrolidone grafted polymethyl amino ethyl methacrylate chitosan obtained in the step S1 and a spinning aid in an acetic acid aqueous solution to form a spinning solution with the total mass concentration of 8-15 percent, preparing nanofiber by high-voltage electrostatic spinning, and crosslinking at 100-155 ℃ to 0.5-3.5 h; S3, constructing a three-dimensional porous structure: soaking the nanofiber obtained in the step S2 in NaHCO 3 solution, then transferring the nanofiber into citric acid solution for foaming to generate CO 2 gas, and performing cleaning, vacuum bubble removal, freezing and freeze drying to obtain the three-dimensional porous nanofiber scaffold; S4, loading musk ketone: and (3) dissolving musk ketone in absolute ethyl alcohol to prepare a solution with the weight percent of 3.5-5%, and soaking the three-dimensional porous nanofiber scaffold obtained in the step (S3) in the musk ketone-ethyl alcohol solution to obtain the intelligent response type nanofiber after the ethyl alcohol volatilizes.
  2. 2. The preparation method of the polyvinylpyrrolidone grafted dimethylamino ethyl methacrylate chitosan nanofiber according to claim 1, wherein in the step S1a, the mole ratio of the brominated chitosan, cuBr/PMDETA, 2-bipyridine and dimethylaminoethyl methacrylate monomer is (0.01-0.05): 0.15-0.3): 0.06-0.1): 10-20.
  3. 3. The preparation method of the polyvinylpyrrolidone grafted polymethyl methacrylate chitosan nanofiber, which is disclosed in claim 1, is characterized in that in the step S1b, the preparation method of the polyvinylpyrrolidone polymer with the end group having a sulfhydryl group is as follows: RAFT polymerization is carried out to prepare PVP precursor, wherein N, N-dimethylformamide is taken as solvent, RAFT reagent 2- (dodecyl trithiocarbonate group) -2-methylpropanoic acid, 1-vinyl-2-pyrrolidone monomer and free radical initiator are added, the mixed solution is subjected to freeze-pump-melt circulation for deoxidization, and stirring reaction is carried out in 65-70 ℃ oil bath under the protection of inert gas for 6-24 h; II, end group functionalization, namely cooling the reaction liquid obtained in the step I to room temperature, adding n-hexylamine, and stirring at room temperature for reaction for 12-24 h; and III, purifying, namely precipitating the reaction liquid obtained in the step II in diethyl ether or n-hexane, collecting solids, dialyzing in deionized water, and freeze-drying to obtain the polyvinylpyrrolidone polymer with the mercapto group at the terminal.
  4. 4. The preparation method of the polyvinylpyrrolidone grafted polymethyl methacrylate chitosan nanofiber according to claim 1, wherein in the step S1b, the graft copolymer obtained in the step S1a and the polyvinylpyrrolidone polymer with the mercapto group at the end group are dissolved in a Tris-HCl buffer solution with pH of 8.0, and the mass ratio of the graft copolymer to the polyvinylpyrrolidone polymer is 1 (1.2-1.8).
  5. 5. The preparation method of the polyvinylpyrrolidone grafted polymethyl amino ethyl methacrylate chitosan nanofiber is characterized in that in the step S2, the spinning aid is pullulan, the mass ratio of the polyvinylpyrrolidone grafted polymethyl amino ethyl methacrylate chitosan to the spinning aid pullulan is 1:2-1:6, and the mass concentration of an acetic acid aqueous solution is 60% -90%.
  6. 6. The preparation method of the polyvinylpyrrolidone grafted polymethyl methacrylate chitosan nanofiber according to claim 1, wherein in the step S2, high-voltage electrostatic spinning control parameters are as follows, the advancing speed is 6.7-26.7 mu L.min -1 , the voltage is 20-28 kV, the receiving distance of a roller receiver is 12-20 cm, the roller rotating speed is 100-300 r.min -1 , the electrostatic spinning temperature is 20-30 ℃, and the humidity is 25-40%.
  7. 7. The preparation method of the polyvinylpyrrolidone grafted polymethyl methacrylate chitosan nanofiber according to claim 1, wherein in the step S3, the concentration of NaHCO 3 is 0.05-0.2M, and the concentration of citric acid solution is 1-5 wt%.
  8. 8. The preparation method of the polyvinylpyrrolidone grafted polymethyl amino ethyl methacrylate chitosan nanofiber is characterized in that in the step S3, the nanofiber is soaked in a foaming solution to be stable at 2-30 min, the air bubble discharging time is 2-6S, the freezing condition is-80 ℃ and is frozen at 1-2 h, the freeze-drying time is 12-24 h, and the freeze-drying temperature is-70 ℃ to-60 ℃.
  9. 9. A polyvinylpyrrolidone grafted poly (dimethylaminoethyl methacrylate) chitosan nanofiber prepared by the preparation method of any one of claims 1-8.
  10. 10. Use of a polyvinylpyrrolidone grafted poly (dimethylaminoethyl methacrylate) chitosan nanofiber according to claim 9 as a dressing in the preparation of a product for treating diabetes wounds.

Description

Polyvinylpyrrolidone grafted polymethyl methacrylate diethylaminoethyl esterification chitosan nanofiber and preparation method and application thereof Technical Field The invention relates to the field of biological medicine, in particular to intelligent response polyvinylpyrrolidone grafted dimethylaminoethyl methacrylate (PVP-g-PDMAEMA) chitosan nanofiber, a preparation method and application thereof. Background Diabetic wounds are difficult to heal due to their unique pathological microenvironment (hyperglycemia, persistent inflammation, alkaline pH, susceptibility to infection). The current dressing based on chitosan has certain hemostatic and antibacterial capabilities, but has single function, cannot actively respond to the change of wound state, and has the problems of uncontrollable drug release, insufficient biocompatibility, poor adaptability to complex microenvironments and the like. Polyvinylpyrrolidone (PVP) has excellent hydrophilicity and biocompatibility, and can effectively resist nonspecific protein adsorption. Poly (2- (dimethylamino) ethyl methacrylate) (PDMAEMA) is a typical pH and temperature dual responsive polymer whose segment conformation is reversibly changeable with changes in ambient pH and temperature. At present, PVP and PDMAEMA are not grafted onto chitosan at the same time, and are reported to be used for constructing intelligent diabetes wound dressing. Disclosure of Invention The invention provides a polyvinylpyrrolidone grafted polymethyl methacrylate diethylaminoethyl esterification chitosan nanofiber, a preparation method and application thereof. The PVP-g-PDMAEMA chitosan nanofiber can actively sense and respond to the change (pH) of the microenvironment of a diabetes wound, can realize the release of drugs according to needs, cooperatively manage wound exudates, and remarkably improve biocompatibility and antibacterial and anti-inflammatory effects. In a first aspect, the invention provides a preparation method of polyvinylpyrrolidone grafted polymethyl methacrylate chitosan nanofiber, which is realized by the following technical scheme. The preparation method of the polyvinylpyrrolidone grafted polymethyl methacrylate chitosan nanofiber comprises the following steps of: s1, synthesizing polyvinylpyrrolidone grafted polymethyl methacrylate (CS-g- (PDMAEMA-g-PVP)) by using the following steps: a. Polymerizing a dimethylaminoethyl methacrylate monomer (DMAEMA) by using an Atom Transfer Radical Polymerization (ATRP) method and taking brominated chitosan (CS-Br) as a macromolecular initiator under a CuBr/PMDETA catalytic system and taking 2, 2-bipyridine as a ligand to obtain chitosan grafted dimethylaminoethyl methacrylate (CS-g-PDMAEMA); b. through click chemistry, dissolving chitosan grafted poly (dimethylaminoethyl methacrylate) and polyvinylpyrrolidone polymer (PVP-SH) with a mercapto group at the end group in Trs-HCl buffer solution with pH of 8.0, and performing magnetic stirring reaction for 24-48 hours at 20-30 ℃ under the protection of nitrogen to obtain polyvinylpyrrolidone grafted poly (dimethylaminoethyl methacrylate) chitosan (PVP-g-PDMAEMA-chitosan); S2, preparing electrostatic spinning nanofiber: dissolving polyvinylpyrrolidone grafted polymethyl amino ethyl methacrylate chitosan obtained in the step S1 and a spinning aid in an acetic acid aqueous solution to form a spinning solution with the total mass concentration of 8-15 percent, preparing nanofiber by high-voltage electrostatic spinning, and crosslinking at 100-155 ℃ to 0.5-3.5 h; S3, constructing a three-dimensional porous structure: soaking the nanofiber obtained in the step S2 in NaHCO 3 solution, then transferring the nanofiber into citric acid solution for foaming to generate CO 2 gas, and performing cleaning, vacuum bubble removal, freezing and freeze drying to obtain the three-dimensional porous nanofiber scaffold; S4, loading musk ketone: and (3) dissolving musk ketone in absolute ethyl alcohol to prepare a solution with the weight percent of 3.5-5%, and soaking the three-dimensional porous nanofiber scaffold obtained in the step (S3) in the musk ketone-ethyl alcohol solution to obtain the intelligent response type nanofiber after the ethyl alcohol volatilizes. By adopting the technical scheme, the diameter 389+/-42 nm of the finally prepared intelligent response nanofiber dressing Musc@CgPgP/P is provided, the porosity is 67.7+/-5.3%, the specific surface area is 192.6+/-7.6 m 2/g, and the musk ketone loading capacity is 1.2-1.5 mg/cm 2. Under slightly alkaline conditions (pH in the range of 7.5-8.0) simulating diabetic wounds, 24 h accumulated release rate 79.4.+ -. 2.6%. The invention combines an atom transfer radical polymerization method with electrostatic spinning and physical adsorption to prepare the intelligent nanofiber dressing with pH responsiveness, which can improve microcirculation disturbance of diabetes wounds and promote the healing of the diabetes wounds. In the step S1a, t