Synthesis, Characterization And Self-assembly Properties Of Novel Amphiphilic Binary Copolymers

Amphiphilic polymers can self-assemble into some aggregates of different shapes applied to the drug carrier systems in solution.Polymeric micelles have emerged as a potential drug carrier because they can improve the bioavailability and lower the toxicity of the loaded drugs.However,most of the polymeric micelles are rapidly cleared from systemic circulation by the Mononuclear Phagocyte System(MPS)and can not achieve the desired therapeutic effect.It has been firmly proved that polymeric micelles with the mimicking structure of cell outer membrane can be misidentified as substance normally present in the human body so as to evade the clearance of the mononuclear macrophage phagocytosis and significantly prolong the drug action time.The experiments showed that amphiphilic copolymers based on 2-methacryloyloxyethyl phosphorylcholine(MPC)polymers can form micelles with mimicking the structure of cell outer membrane in certain conditions,and these micelles can effectively decrease the extent of platelet adhesion and protein adsorption,and more importantly,this biomembrane mimetic micelle can escape from the removal of MPS.So far,most of researches on MPC copolymer micelles as drug carriers focused on block copolymers synthesized Atom Transfer Radical Polymerization(ATRP).However,ATRP method is not only complicated but the copper catalyst could not be remove completely,which may seriously affect the biocompatibility of the MPC polymer.Therefore,it has important theoretical and practical significance to study the random copolymers synthesized from free radical polymerization and their application in the drug delivery system.The research is mainly composed of the following aspects:(1)Poly(?-caprolactone)macromonomer,MaPCL was synthesized by ring-opening polymerization(ROP)of e-caprolactone(CL)at the hydroxyl group of hydroxyethyl methacrylate(HEMA)using stannous octoate as catalyst.Afterwards copolymers of P(MPC-co-MaPCL)were synthesis by solution polymerization.To establish structure-function relationships,three different polymers were synthesized.1H NMR,FT-IR,GPC and XPS were used to characterize the structure and purity of the copolymers.The results indicated that the synthesis was successful.(2)Self-assembly behaviors of copolymers P(MPC-co-MaPCL)s were studied using by solvent evaporation method.The results of dynamic light scattering(DLS)and scanning electron microscopy(TEM)showed that the average particle size of the polymeric micelles was 100-200 nm with core shell structure.The cytotoxicity of polymeric micelles with cell membrane mimetic structure was zero or one degree,indicating good biocompatibility.The in vitro results for phagocytosis by murine peritoneal macrophage showed that the uptake probability of polymeric micelles containing PC groups were greatly reduced,and the higher of the PC content,the lower of the uptake rate.(3)In the drug loading and releasing experiment,adriamycin(ADR)was chosen as the hydrophobic model drug and was incorporated into the core of the micelles by solvent evaporation method.The effect of several parameters during the vitro release experiment like pH,the initial dosage et al was studied.The results of vitro release experiment of copolymer P(MPC-co-MaPCL)nanomicelles showed that this kind of micelles should be an ideal sustained release system for ADR and some hydrophobic drugs released.From all the results we can get the conclusion that the MPC random copolymers owed great potential as drug delivery carrier.