Synthesis And Properties Of A Multiplely Biomimetic Phospholipid Copolymer

In clinical applications,the conventional still have problems of infection,coagulation and hyperplasia to a certain extent.Biocompatible polymer coating designed for solving these problems provides an effective way.In this paper,novel biomimetic polymers bearing phosphorylcholine,dpamine and cholesterol groups were synthesized and coated on different substrates by the attached dopamine,which is the key ingredient of marine mussel adhesion proteins.When the polymer was immobilized on a surface,the phosphorylcholine and cholesterol groups attached on the other side chains form a cell outer membrane mimetic coating automatically.The formed polymer surface stability and biocompatibility were investigated systematically.This main work of this thesis includes the following three aspects:(1)Synthesis and Characterization of the multiple biomimetic polymer PMNCC.?The synthesis includes the following four parts.First,the synthesis of active ester monomer MEONP.Then AIBN as initiator,MEONP and 2-methylacryloyloxyethyl phosphorylcholine(MPC)was copolymerized by random copolymerization to synthesize the copolymer bearing phosphorylcholine and active ester groups(PMN).Cholesteryl chloroformate was reacted with ethylene diamine at a low temperature to achieve cholesterol's amination.Finally,the active ester side chains were coupled efficiently with primary amine groups of both dopamine and diamine aminated cholesterol,producing the multiple biomimetic polymers PMNCC.1H-NMR was employed to determine the structure and composition of the polymer.? Folic acid-functioned PMNCC as tumor targeting amphophilic polymers(PMMCF).Diamine aminated folic acid and cholesterol were prepared as above mentioned.The active ester side chains of PMN were grafted with cholesterol and folic acid the amination reaction.The graft density of folate ligand in PMNCF polymers with measured by 1H-NMR to be 30%,17%and 8%in samples of 30%FA-PMNCF,17%FA-PMNCF and 8%FA-PMNCF respectively.(2)Preparation of novel amphiphilic polymer micelles.? Preparation of amphiphilic polymer PMNCC self-assembled micelles.PMNCC tetrahydrofuran solution was added dropwise to ultrapure water with a slower rate stirring,and self-assembled micelles was prepared by the mans of solvent evaporation method.The micelles shwed a small hydrodynamic diameter(approximately 30?100 nm),a uniform distribution(PDI=0.1?0.2)and excellent stability(no deposition after 60 d storage).In addition,since the preparation process is simple and clean,it should have a broad application in the biomedical field.?Preparation of the polymer micelles of PMNCF.Dimethyl sulfoxide dissolved PMNCF was droped in slowly stirred ultrapure water.The micelles formed by self-assembly showed hydration diameter of number-average particle size from 60 run to 200 nm(PDI = 0.2?0.3).The number average particle size increaseed with folate concentration of the polymer.The biomimetic polymer micelles bearing tumor targeting folate ligand provides a new approach for the study of targeted modification of nano carriers.(3)Construction,stability,physicochemical and biological properties testing of the multiple biomimetic polymer coating.The multiple biomimetic polymer was dissolved in the mixed solvent consists of tetrahydrofuran and water and drop-coated on coverslip,stainless steel,polycarbonate and polytetrafluoroethylene surfaces.Dynamic contact angle measurements showed that the difference in contact angles among different substrates disapeared after the coating.The same contact angles of an identical polymer coating on different substrates reveals that the substrate nature was completely masked by the polymer film.In order to verify the stability of the coating,it was soaked in 75%alcohol for 12h,soaked in hot water,ultrasonicated in PBS for 2h and heated air.The unchanged dynamic contact angles indicated excellent stability of modified coating.Protein adsorption experiment results showed that the bovine serum albumin(BSA)and bovine serum fibrinogen(Fg)adsorption on the modified glass,polycarbonate and steel have reduced by more than 85%compared with the non-modified surfaces.The amount of platelet adhesion was reduced by more than 95%,indicating a excellent hemocompatibility.