Development of a thermosensitive grafted drug delivery system—synthesis and characterization of NIPAAm‐based grafts and hydrogel structure

A thermosensitive grafted hydrogel was investigated for heating‐activated drug release. The hydrogel was created by grafting oligomers of N‐isopropylacrylamide‐co‐acrylamide (AAm) to a poly(2‐hydroxyethyl methacrylate), or PHEMA, hydrogel. N‐Isopropylacrylamide‐co‐AAm oligomers were synthesized with a range of compositions to raise the lower critical solution temperature (LCST) above physiological temperature. PHEMA hydrogels with these thermosensitive grafts were synthesized by free‐radical solution polymerization, using an acrylated version of the oligomers. The oligomers were characterized for their molecular weight, LCSTs, and rate of response to a change in temperature. With the flexibility in tuning their properties by varying reaction parameters, these oligomers present possibilities in several fields, including drug delivery. The impact of cross‐linking agent type and the amount and presence of grafts on the polymer network structure was found by determining the hydrogel mesh sizes. PHEMA gels cross‐linked with methylenebisacrylamide had larger mesh sizes than those cross‐linked with ethylene glycol dimethacrylate. Increasing amounts of cross‐linking agent decreased mesh sizes. LCSTs exhibited by oligomers were slightly lower than those exhibited by polymer gels of the same composition. The grafting reaction was found to have only a slight impact on the hydrogel mesh size. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011