A novel hydrogel with dual temperature and pH responsiveness loading nanostructured lipid carriers as an ophthalmic delivery system: enhanced trans-corneal permeability and bioavailability of nepafenac
The aim of the current study was to encapsulate nepafenac (NP) in the in situ hydrogel modified nanostructured lipid carrier (NP-NLC-Gel) nanoparticles as an efficient ocular delivery system to improve its transcorneal penetration and precorneal retention. NP-NLC nanoparticles were prepared by melt emulsification method. The synthesized hydrogel, composing of poloxamer and carboxymethyl chitosan, was liquid solution at low temperature and pH and then turned to semisolid on the surface of cornea. The enhanced transcorneal penetration of the NLC was evaluated using isolated rabbit corneas, with significantly increased apparent permeability coefficient being 2.36-fold of the NP eye drops (p < 0.05). Precorneal retention assessed by fluorescence imaging technology in vivo showed that NP-NLC-Gel had longer retention time on corneal surface compared with the NP eye drops. In vivo ocular tolerance study indicated that there was no difference in irritation between the NP eye drops and the NP-NLC-Gel. The concentration of nepafenac in aqueous humor and lacrimal fluid was determined using HPLC. The AUC0−∞ of NP-NLC-Gel was increased up to 6.3- and 1.9-fold respectively as compared with the eye drops. In conclusion, NP-NLC-Gel possesses a greater potential as an ocular drug delivery system comparing with the NP eye drops.