Synthesis And Application Of Biocompatible And PH-Responsive Triblock Copolymers

Biodegradable amphiphilic block copolymers are widely used in biomedical field including drug/gene delivery system and tissue engineering because of their excellent biocompatibility and biodegradability. The present thesis focused on two kinds of pH-responsive and amphiphilic triblock copolymers synthesized by a combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). Their self-assembly behavior in aqueous solution was studied and their potential applications in drug and gene delivery were also preliminary investigated. The main contents of this thesis are listed as follows:Part 1. Amphiphilic triblock copolymer mPEG-b-PCL-b-PDMAEMAPolyethylene glycol monomethyl ether (mPEG) was first used to initiate the ring-opening polymerization ofε-caprolactone (ε-CL) in the presence of stannous octoate [Sn(Oct)2], resulting in an amphiphilic block copolymer mPEG-b-PCL, which was then converted to ATRP macroinitiator mPEG-b-PCL-Br by the reaction with 2-bromoisobutyryl bromide. The amphiphilic triblock copolymer mPEG-b-PCL-b- PDMAEMA was subsequently prepared through the ATRP of 2-(dimethylamino)ethyl methacrylate (DMAEMA) using the mPEG-b-PCL-Br as initiator. FT-IR, 1H NMR, GPC and TGA measurements were utilized to characterize the chemical structure, composition, molecular weight and molecular weight distribution. Fluorescence probe method, TEM and HPPS analyses were applied to study the self-assembly behavior of the amphiphilic triblock copolymer in different pH buffer solutions, which indicated that they were affected by the length of hydrophilic/hydrophobic blocks, pH values of water phase, etc. The polymer stability assay showed that the copolymer was not stable in acidic condition due to the hydrolization of ester bonds in PCL block; while in neutral condition, the copolymer was more stable. Cell toxicity tests (MTS assay) indicated that the copolymers were less toxic to KB and HEK293 cells than branched PEI (25 kDa). In addition, agarose gel retardation assays demonstrated that these cationic nanoparticles can effectively condense plasmid DNA. In vitro release of Naproxen from these nanoparticles in different pH buffer solutions was conducted, demonstrating that higher PCL content would result in the higher drug loading content and lower release rate. And the higher pH buffer solution, the faster release rate.Part 2. Amphiphilic triblock copolymer PEEP-b-PCL-b-PDMAEMAA bifunctional initiator 2-hydroxyethyl-2-bromo-isobutyrate (HEBI) and a cyclic monomer 2-ethoxy-2-oxo-1, 3, 2-dioxaphospholane (EEP) were first synthesized. HEBI was then used to initiate the ring-opening polymerization ofε-CL using Sn(Oct)2 as catalyst to prepare the HEBI-PCL homopolymer, which was then utilized to initiate the ring-opening polymerization of EEP, resulting in the diblock copolymer PEEP-b-PCL. Finally, the amphiphilic triblock copolymer PEEP-b-PCL-b-PDMAEMA was obtained by the ATRP of DMAEMA using PEEP-b-PCL as the macroinitiator. 1H NMR and GPC methods were utilized to characterize the chemical structure, molecular weight and molecular weight distribution, which showed that the HEBI-PCL homopolymer and PEEP-b-PCL diblock copolymer have been successfully synthesized.