Nanostructured lipid carrier-based pH and temperature dual-responsive hydrogel composed of carboxymethyl chitosan and poloxamer for drug delivery

The aim of this study was to develop a novel nanostructured lipid carrier (NLC) based dual-responsive hydrogel for ocular drug delivery of quercetin (QN). NLC loaded with quercetin (QN-NLC) was prepared using melt-emulsification combined with ultra-sonication technique. A three-factor five-level central composite design (CCD) was employed to optimize the formulation of QN-NLC. The optimized QN-NLC presented a particle size of 75.54 nm with narrow size distribution and high encapsulation efficiency (97.14%).QN-NLC was characterized by TEM and DSC. In addition, a pH and temperature dual-responsive hydrogel composed of carboxymethyl chitosan (CMCS) and poloxamer 407(F127) was constructed by a cross-linking reaction with a naturally occurring nontoxic crosslinking agent genipin (GP). FT-IR was employed to demonstrate that F127/CMCS hydrogel was successfully synthesized. The results of SEM analysis and swelling experiments indicated that F127/CMCS hydrogel was both temperature-responsive and pH-responsive. From the results of In vitro release studies, dual temperature and pH responsiveness of the hydrogel was demonstrated, and 80.52% of total quercetin was released from the QN-NLC based hydrogel (QN-NLC-Gel) within 3 days, revealing QN-NLC-Gel released drug sustainably. Taken together, the developed NLC-based hydrogel is a promising drug delivery system for the ophthalmic application.