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

• Main Authors: Yibin Yu, Ruoxi Feng, Jinyu Li, Yuanyuan Wang, Yiming Song, Guoxin Tan, Dandan Liu, Wei Liu, Xinggang Yang, Hao Pan, Sanming Li
• Format: Article
• Language: English
• Published: Elsevier 2019-07-01
• Series: Asian Journal of Pharmaceutical Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S181808761830521X

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. BNNLC 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 BNNLC gel can prolong the release of baicalin comparing with BN eye drops and BNNLC. Ex vivo cornea permeation study was evaluated using Franz diffusion cells. The apparent permeability coefficient (Papp) of BNNLC gel was much higher (4.46-fold) than that of BN eye drops. Through the determination of corneal hydration levels, BNNLC 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. Keywords: Ocular drug delivery, Nanostructured lipid carrier, Semi-IPN hydrogel