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 37 °C 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. Copyright © 2004 Society of Chemical Industry