Thermosensitive hydrogel containing sertaconazole loaded nanostructured lipid carriers for potential treatment of fungal keratitis

Abstract

This study was conducted to develop an <i>in situ</i> thermosensitive gel containing sertaconazole-loaded nanostructured lipid carriers (NLCs) for prolonged ocular drug delivery. To this end, sertaconazole-loaded NLCs (sertaconazole-NLCs) were prepared by emulsification solvent-diffusion method and the effects of different formulation variables were assessed using the fractional factorial design. Then, optimized sertaconazole-NLCs were incorporated into the pluronic F127 (PF127)/hydroxy propylmethylcellulose (HPMC) K4M hydrogel. The formulations were examined for pH, gelation temperature, rheological properties, <i>in vitro</i> permeation studies, and anti-fungal activity. The optimized sertaconazole-NLCs showed a mean particle size of 272.40 nm, encapsulation efficiency of 89.97%, zeta potential of 12.9 mV, and polydispersity index of 0.31. All the <i>in situ</i> formulations had acceptable pH, ranging from 5.89 to 6.28. The gelation temperature of the optimized formulation was 35.1 °C after dilution with simulated tear fluid (STF). Sertaconazole-NLCs showed a higher antifungal activity and permeation through the bovine cornea compared to the free drug and the <i>in situ</i> gel formulation. The cornea penetration of sertaconazole for the <i>in situ</i> gel of NLCs was also comparable to that for free drug. The obtained results indicated that the prepared nanocomposite system may have potential for treatment of fungal keratitis.