Synthesis And Characterization Of Amphiphilic Polymers Bearing Cholesterol Moieties

Insulin-dependent diabetes is a fatal disease impacting human life which ascribes to over-thresholded glucose level. Glucose-responsive nanoparticles can mimic pancreatic function, passively "secrete" loaded insulin corresponding to fluctuant blood glucose level. This paper proclaimed a new synthetic strategy to synthesis macro chain transfer agents with dithiocarbamate single terminated or both terminated using Click chemistry. We synthsised a series of amphiphilic diblock polymers containing cholesterol, triblock polymers having phenylborate ester and random copolymers with cholesterol and phenylborate ester moieties. We studied FITC-INS release behavior of glucose-responsive nanoparticles in PBS.1. First, we obtaind amphiphilic block polymers mPEG5000-b-PDEGCholA-CPAD using macro chain transfer agents mPEG5000-CPAD induced RAFT polymerization. Dithiocarbamate terminated polymer was transfered to thiol group through aminolysis by ethanol amine, and both block polymers were characterized by NMR as well as GPC.2. We synthsised marco chain transfer agents (CPAD-PEG4000-CPAD) with both dithiocarbamate in the terminal using catalyst PMDETA/CuBr, then we got a series of glucose-responsive triblock polymers PPBDEMA-b-PEG4000-b-PPBDEMA followed with NMR and GPC analysis. Critical micelle concentration (CMC) was measured using pyrene fluorescence probe. Triblock polymers nanoparticles with individual concentration were prepared by self-assembly in water. The analytical result indicated that only triblock polymer with a degree of polymerization of 103 can self-assembled into a stable nanoparticles solution, which can achieve a controlled FITC-INS release in 0.01 M pH7.4 PBS during experiment period with a long lagtime.3. We prepared a series of copolymers (P(PBDEMA-co-DEGCholA)-PEG4000-P(PBDEMA-co-DEGCholA)) bearing a plenty of cholesterol group and phenylborate ester. Structure of random copolymers was determined by NMR and GPC. Moreover, stable nanoparticles were made at the concentration of 0.6 mg/mL, the result showed that copolymers with cholesterol moiety can achieve controlled release of FITC-INS in 0.03 M PBS at pH7.4 with a degree of polymerization 60/38 due to their special construction.