Copolymers of N-isopropylacrylamide, HEMA-lactate and acrylic acid with time-dependent lower critical solution temperature as a bioresorbable carrier

Copolymers of N-isopropylacrylamide (NIPAAm), 2-hydroxyethyl methacryl lactate (HEMA-lactate) and acrylic acid (AAc) were prepared, with varying mole ratios of monomers, to develop a bioresorbable in-situ-gelling material with a time-dependent lower critical solution temperature (LCST). The synthesized copolymers were characterized by nuclear magnetic resonance, gel permeation chromatography and differential scanning calorimetry. In 0.1 M phosphate-buffered saline solution of pH 7.4, these copolymers had an LCST below body temperature. The LCST decreased as the HEMA-lactate content of the copolymers was increased. Furthermore, in these conditions, the LCST of the copolymers exhibited time-dependent properties, due to hydrolysis of the HEMA-lactate. As the HEMA-lactate hydrolyzed, the copolymers became more hydrophilic, thereby leading to an increase in LCST. This hydrophilicity caused copolymers of approximately 6 mol% of AAc to exhibit an LCST above body temperature after hydrolysis. In neutral solution, copolymers with varying mol% of AAc saw their LCST rise above 37degreesC within one to ten days, depending upon the HEMA-lactate/NIPAAm ratio, due to the complete hydrolysis of the HEMA-lactate. The above properties indicate that these copolymers would be useful for drug delivery because their variable LCST makes them bioresorbable. (C) 2004 Society of Chemical Industry.