C h a p t e r 25
Synthesis and Characterization of Thermoreversible, Protein-Conjugating Polymers Based on N-Isopropylacrylamide Hasan Uludag and Xiao-Dong Fan Department of Biomedical Engineering, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada
Thermoreversible, protein-conjugating polymers are being explored as drug carriers for controlled delivery of therapeutic proteins. Such polymers can be designed so that they (i) can conjugate to proteins without crosslinking agents, (ii) are soluble at a low temperature (so that chemical manipulations can be carried out in a solution state), and (iii) are insoluble at the physiological temperature to form a gelled state at a site of application. This study was intended to engineer thermoreversible N-isopropyl-acrylamide (NiPAM) polymers that contain protein-reactive N-acryloxysuccinimide (NASI) and hydrophobic methyl methacrylate (MMA) and ethyl methacrylate (EMA) units. NASI, M M A and EMA units were all shown to effectively reduce the lower critical solution temperature (LCST) of the polymers. NASI component was shown to undergo pH-dependent hydrolysis which can significantly influence the LCST. In experiments designed to assess the stability of polymer gels, gel stability was found to be inversely correlated with the LCST. In experiments designed to assess gel formation, NASI was found to have an unstabilizing effect on hydrogel formation, and M M A and EMA (
