Synthesis via RAFT polymerization of thermo- and pH-responsive random copolymers containing cholic acid moieties and their self-assembly in water

Here we report the design and synthesis of polymers containing cholic acid pendant groups, a major bile acid synthesized in the liver from cholesterol. Random copolymers derived from 2-(methacryloyloxy)-ethyl cholate (MAECA) with polyethylene glycol methyl ether methacrylate (PEGMA) and N,N-dimethylaminoethyl methacrylate (DMAEMA) have been synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Compositions of co-monomers in the copolymers were determined by H-1 NMR spectroscopy, which were further used to determine reactivity ratios of the monomers using the extended Kelen-Tudos method at high conversions. Copolymers from MAECA with PEGMA (P(MAECA-co-PEGMA)) series displayed lower critical solution temperatures (LCSTs) up to 23% MAECA content in the copolymer, which was studied by UV-visible spectroscopy. Both thermo- and pH-responsiveness were observed for the P(MAECA-co-DMAEMA) copolymers with an MAECA unit in the copolymer up to 11.8%. The critical aggregation concentration (CAC) of water soluble copolymers was determined by fluorescence spectroscopy. Self-assembly of random copolymers was investigated by H-1 NMR spectroscopy, dynamic tight scattering (DLS), atomic force microscopy (AFM) and scanning electron microscopy (SEM), which indicated micellar structures in water from cholic acid based random copolymer. The polymeric aggregates were further explored for their drug encapsulation capabilities in aqueous medium using nite red as a hydrophobic model compound.