Corneal targeted Sertaconazole nitrate loaded cubosomes: Preparation, statistical optimization, in vitro characterization, ex vivo permeation and in vivo studies

摘要

Sertaconazole nitrate (STZ) is a poorly soluble antifungal drug commonly used for treating fungal skin infections. Introducing it as a new treatment option for the management of fungal keratitis, requires the development of a delivery system capable of targeting the infected cornea with an adequate STZ concentration. Hence, Sertaconazole nitrate loaded cubosomes (STZ-CUBS) were prepared, characterized and optimized based on a 3(3) central composite face-centred design. Optimized formulation (CUB-opt) showed maximum desirability (0.905), with solubilization efficiency (SE%) of 94.50 +/- 0.51%, particle size (PS) of 216.55 +/- 2.33 nm, polydispersity index (PDI) of 0.229 +/- 0.11 and zeta potential (ZP) of 34.00 +/- 6.93 mV. Under the transmission electron microscope, it showed discrete cubic shaped structures. Moreover, it exhibited a promising mucoadhesive behavior, terminal sterilization stability, and storage stability. Ex vivo corneal permeation study revealed its ability to enhance the steady state flux (J(ss)) and the permeability coefficient (K-P) of STZ, compared to STZ-suspension. Finally, CUB-opt formulation was found to be safe on the corneal tissues in the in vivo corneal tolerance study, and demonstrated a superior corneal penetration power in the in vivo corneal uptake study.