Synthesis and characterization of thermosensitive and pH-sensitive poly (N-isopropylacrylamide-acrylamide-vinylpyrrolidone) for use in controlled release of naltrexone

Abstract

In this article N-isopropylacrylamide (NIPAAm)-acrylamide (AAm)-vinyl pyrrolidone (VP) terpolymers were prepared using free radical copolymerization method by varying feed ratios of monomers. The composition ratio and structure of polymer were determined by NMR and FTIR. The glass transition temperature was examined by DSC. The thermo-responsive behaviors of polymeric solutions were investigated by turbidimetry using UV-Visible spectroscopy. The sol-gel transition of the polymer solutions occurred reversibly within 1 min in response to the temperature. By alternating the monomer feed ratio, the synthesized terpolymers had their own distinctive lower critical solution temperature (LCST). In addition to the thermosensitivity, the terpolymers also showed a response to pH changes. The increase in ionic strength of the buffer solution with addition of salt lowered the LCST of the polymers. The ability to shift the phase transition temperature of the terpolymers provided excellent flexibility in tailoring transitions for specific uses. Swelling experiments were performed on the terpolymer disks in buffer solutions with different pH and ionic strength at varying temperature. We investigated naltrexone release as a model drug in phosphate buffer. Drug loading efficiency was varying from 8.75 to 550%. Gel composition, pH, and ionic concentration affected the drug loading, Finally in vitro drug release studies at 36-37 degrees C indicating 35-70% naltrexone release from terpolymers at the end of 30 days. In addition, these gels sustained naltrexone release for 30 days. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 84A: 919-928, 2009