A hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier ocular drug delivery platform

Abstract

The objective of this study was to develop a novel hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier (NLC) drug delivery platform. An ophthalmic anti-inflammatory drug, baicalin (BN) was chosen as the model drug. BNNLC was prepared using melt-emulsification combined with ultra-sonication technique. Additionally, a dual pH- and thermo-sensitive hydrogel composed of carboxymethyl chitosan (CMCS) and poloxamer 407 (F127) was fabricated by a cross-linking reaction with a nontoxic crosslinker genipin (GP). GP-CMCS/F127 hydrogel was characterized by FTIR, NMR, XRD and SEM. The swelling studies showed GP-CMCS/F127 hydrogel was both pH- and thermo-sensitive. The results of in vitro release suggested BNNLC gel can prolong the release of baicalin comparing with BN eye drops and BNNLC. Ex vivo cornea permeation study was evaluated using Franz diffusion cells. The apparent permeability coefficient (Papp) of BNNLC gel was much higher (4.46-fold) than that of BN eye drops. Through the determination of corneal hydration levels, BNNLC gel was confirmed that had no significant irritation to cornea. Ex vivo precorneal retention experiments were carried out by a flow-through approach. The results indicated that the NLC-based hydrogel can prolong precorneal residence time. In conclusion, the hybrid NLC-based hydrogel has a promising potential for application in ocular drug delivery.