Younes, N. F., S. A. Abdel-Halim, and A. I. Elassasy, "Solutol HS15 based binary mixed micelles with penetration enhancers for augmented corneal delivery of sertaconazole nitrate: optimization, in vitro, ex vivo and in vivo characterization.", Drug delivery, vol. 25, issue 1, pp. 1706-1717, 2018 Nov. Abstract

Keratomycosis is a serious corneal disease that can cause a permanent visual disability if not treated effectively. Sertaconazole nitrate (STZ), a novel broad spectrum antifungal drug, was suggested as a promising treatment. However, its utility in the ocular route is restricted by its poor solubility, along with other problems facing the ocular delivery like short residence time, and the existing corneal barrier. Therefore, the objective of this study was to formulate STZ loaded binary mixed micelles (STZ-MMs) enriched with different penetration enhancers using thin-film hydration method, based on a 3.2 mixed factorial design. Different formulation variables were examined, namely, type of auxiliary surfactant, type of penetration enhancer, and total surfactants: drug ratio, and their effects on the solubility of STZ in MMs (S), particle size (PS), polydispersity index (PDI), and zeta potential (ZP) were evaluated. STZ-MMs enhanced STZ aqueous solubility up to 338.82-fold compared to free STZ. Two optimized formulations (MM-8 and MM-11) based on the desirability factor (0.891 and 0.866) were selected by Design expert software for further investigations. The optimized formulations were imaged by TEM which revealed nanosized spherical micelles. Moreover, they were examined for corneal mucoadhesion, stability upon dilution, storage effect, and ex vivo corneal permeation studies. Finally, both in vivo corneal uptake and in vivo corneal tolerance were investigated. MM-8 showed superiority in the ex vivo and in vivo permeation studies when compared to the STZ-suspension. The obtained results suggest that the aforementioned STZ loaded mixed micellar system could be an effective candidate for Keratomycosis-targeted therapy.

Younes, N. F., S. A. Abdel-Halim, and A. I. Elassasy, "Corneal targeted Sertaconazole nitrate loaded cubosomes: Preparation, statistical optimization, in vitro characterization, ex vivo permeation and in vivo studies.", International journal of pharmaceutics, vol. 553, issue 1-2, pp. 386-397, 2018 Dec 20. Abstract

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 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) and the permeability coefficient (K) 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.