Thermosensitive polylactide-glycolide delivery systems for treatment of narcotic addictions

Abstract

Environmental switches may be fabricated for the controlled release of pharmaceutical drug using a thermally responsive polymer with the intrinsic chemical and physical nature of stimuli-sensitive smart materials. Particularly, much attention has been paid to the biomedical applications of poly(N-isopropyl acrylamide) (PNIPAAm) because of its unique reversible transition at a specific lower critical solution temperature (LCST).Thermally sensitive block copolymers, poly(N-isopropyl acrylamide-b-poly(L-lactide-co-glycolide) (PNIPAAm-b-PLGA), and polyethylene glycol-poly (lactide-co-glycolide) (PEG-PLGA) triblock copolymers with different compositions and length of PLGA block were synthesized via ring-opening polymerization of lactide and glycolide in the presence of OH-terminated PNIPAAm or PEG. The composition and structure of the polymer were determined by NMR and FTIR. The effect of important factors, such as ionic strength, PH, and polymer concentration on the phase transition behavior of temperature-sensitive polymers, were investigated by cloud point measurements. The resulting thermosensitive polymers were used for the entrapment of a narcotic antagonist drug, naltrexone, as the model drug. The loading efficiency and drug release behavior of naltrexone-loaded hydrogels were investigated. The naltrexone loaded thermosensitive polymers were able to sustain the release of naltrexone for different periods of time, depending on the polymer composition, and concentration. In vitro release studies showed that these thermosensitive polymers are able to deliver naltrexone in biologically active forms at a controlled rate for 3-8 weeks. Copyright (C) 2009 John Wiley & Sons, Ltd.