Novel Thermosensitive Hydrogel Composites Based on Poly(D,L-lactide-co-glycolide) Nanoparticles Embedded in Poly(N-isopropyl acrylamide) with Sustained Drug-Release Behavior

To reach sustained drug release, a new composite drug-delivery system consisting of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) embedded in thermosensitive poly(N-isopropyl acrylamide) (PNIPAAm) hydrogels was developed. The PNIPAAm hydrogels were synthesized by free-radical polymerization and were crosslinked with poly(ethylene glycol) diacrylate, and the PLGA NPs were prepared by a water-in-oil-in-water double-emulsion solvent-evaporation method. The release behavior of the composite hydrogels loaded with albumin-fluorescein isothiocyanate conjugate was studied and compared with that of the drug-loaded neat hydrogel and PLGA NPs. The results indicate that we could best control the release rate of the drug by loading it to the PLGA NPs and then embedding the whole system in the PNIPAAm hydrogels. The developed composite hydrogel systems showed near zero-order drug-release kinetics along with a reduction or omission of initial burst release. The differential scanning calorimetry results reveal that the lower critical solution temperature of the developed composite systems remained almost unchanged (<1 degrees C increase only). Such a characteristic indicated that the thermosensitivity of the PNIPAAm hydrogel was not distinctively affected by the addition of PLGA NPs. In conclusion, an approach was demonstrated for the successful preparation of a new hybrid hydrogel system having improved drug-release behavior with retained thermosensitivity. The developed systems have enormous potential for many biotechnological applications. (c) 2014 Wiley Periodicals, Inc.