Preparation,Glucose Responsiveness And Drug Release Of Amphiphilic Block Copolymer Based On PBA

In recent years,the high incidence of diabetes has become one of the major health hazards,so it is extremely urgent to develop relevant hypoglycemic drug delivery materials.Glucose responsive micelles based on phenylboric acid（PBA）have attracted extensive attention due to their biocompatibility and low cost.In order to solve the problem that the p Ka of PBA polymer conforms to the actual physiological environment of human body（p H=7.4,37℃）,and realize the goal of intelligent controlled controlled release of drugs on demand,this project uses RAFT polymerization to synthesize PBA-based temperature,p H and glucose responsive intelligent controlled controlled release drug delivery materials.The structure and properties of the materials were characterized by ¹H-NMR,FT-IR,TEM,DLS,UV and other test methods,the effects of the length of hydrophilic and hydrophobic segments and the amount of PVA on glucose response and insulin load release were investigated.The main research content of this paper is summarized as follows:（1）The p Ka of PBA-based polymers（p H=7.4）was reduced by the complexation of nitrogen and boron atoms.Diblock copolymerization of 3-acrylamide-phenylboric acid with diethylaminoethyl methacrylate（DEAEMA）was carried out by RAFT polymerization.The effects of hydrophilic and hydrophobic chain length on micellar behavior and glucose response of amphiphilic block copolymers were systematically studied.The results showed that the p Ka of the synthetic amphiphilic block copolymer p（AAPBA-B-DEAEMA）decreased from 8.4 to 7.0 with the increase of the length of the hydrophilic block copolymer PDEAEMA,which showed glucose response under the actual physiological environment（p H=7.4）.The p(AAPBA₅₆-b-DEAEMA₆₀)micelles showed good glucose response in 1-3mg/m L glucose phosphate buffer solution,and their D_Hresponse increased from 385.2 nm to695.3 nm with the increase of glucose concentration.Meanwhile,D_Hof the nanomicelles increased rapidly with the increase of the hydrophilic segment of PDEAEMA.In addition,insulin activity of the synthesized two-block copolymer remained good before and after release.（2）A series of ternary block copolymer p（AAPBA-b-DEAEMA-NIPAM）was synthesized via RAFT polymerization by adding the thermosensitive monomer chain of PNIPAM,and complex micelles were prepared by complexing with polyvinyl alcohol（PVA）.The effects of PNIPAM chain length and PVA dosage on insulin release performance of compound micelle were systematically discussed.The results showed that with the increase of PNIPAM chain length,the drug loading and encapsulation rate of micelle loaded insulin were significantly increased,and the maximum polymerization degree of PAAPBA was 43for p(AAPBA₄₃-b-DEAEMA₃₄-b-NIPAM₃₉)terpolymer increased to 42.3%and 21.2%,respectively.It also increased with the increase of PVA content,and the maximum value reached 46.2%and 23.1%,respectively.Secondly,compound micelles have intelligent insulin release properties.Compared with the two-block copolymer p(AAPBA₄₃-b-DEAEMA₃₄),compound micellar PBA-co-PVA decreased insulin release from 45.8%to 16%at normal blood glucose level（1 mg/m L）,and its value decreased with the increase of PNIPAM and PVA contents.Insulin release from compound micelles decreased from 27.7%to 16%.At the hyperglycemia level（3 mg/m L）,the insulin release rate of compound micelles was significantly increased,and the cumulative drug release reached the maximum 65.8%.