Development of NIPAAM-based thermosensitive, injectable and biodegradable copolymers for controlled release of anti-cancer drug

Thermosensitive, injectable and biodegradable N-isopropylacrylamide-based copolymer, poly(N-isopropylacrylamide-co-dimethyl-gamma-butyrolactone acrylate-coacrylic acid), P(NDBA), was synthesized with varying feed ratio of three monomers. The materials have been characterized by Differential Scanning Calorimetry (DSC), Gel Permeation Chromatography (GPC) in conjunction with Static Light Scattering (SLS), Fourier Transform Infrared (FTIR) spectroscopy, 1H Nuclear Magnetic Resonance (1H NMR), acid titration, cloud point test, and percentage mass loss. It was found that the lower critical solution temperature (LCST) of the synthesized copolymer can be manipulated to be between room temperature and body temperature by varying the feed ratio of dimethyl-gamma-butyrolactone acrylate (DBA) and acrylic acid (AAc). The copolymer has a time-dependent LCST property and the degradation time can be manipulated to be from two weeks to two months. These properties indicated that the material can be a good candidate material for controlled drug release and tissue engineering applications.;The in vitro cytotoxicity and in vivo biocompatibility test showed that these materials have a low cytotoxic effect to fibroblast cells in vitro and would healing process was observed after subcutaneous injection in vivo. The in vitro drug release study showed a sustained release pattern from the synthesized copolymer. The anti-tumor efficacy test showed a significant slow tumor growth after the subcutaneous injection of the suspended drug in the copolymer.