5-Fluorouracil- and Sesamol-Loaded Transliposomal Gel for Skin Cancer: In Vitro, Ex Vivo, and Dermatokinetic...

This study explores a novel approach to managing skin conditions through a combination therapy utilizing a phospholipid-enriched edge activator-based nanoformulation. 5-Fluorouracil (5-FU)- and sesamol (SES)-loaded transliposomes (FS-TL) were developed using a thin film hydration method and optimized using Box-Behnken Design. FS-TL characterization indicated a vesicle size of 165.6 ± 1.1 nm, polydispersity index of 0.28 ± 0.01, and a zeta potential of -33.17 ± 0.9 mV, and the percent entrapment efficiencies for 5-FU and SES were found to be 63.16 ± 1.07% and 75.60 ± 3.68%, respectively. The drug loading percents for 5-FU and SES were found to be 5.87 ± 0.099% and 7.03 ± 0.34%, respectively. The morphological studies exhibit the distinctive spherical shape of the nanoformulation. The in vitro drug release demonstrated sustained release with 82.52 ± 1.2% and 86.28 ± 1.3% releases for 5-FU and SES, respectively. The ex vivo skin permeation exhibited 81.04 ± 2.1% and 78.03 ± 1.7% for 5-FU and SES. Confocal laser microscopy scanning (CLSM) revealed a deeper formulation penetration (30.0 μm) of excised mice skin membranes than for a standard rhodamine solution (10.0 μm). The dermatokinetic investigation revealed that FS-TL gel has significantly higher concentrations of 5-FU and SES (p < 0.001). The efficacy of FS-TL (p < 0.05) in eradicating the A431 melanoma cell line was satisfactory. These findings suggest the potential of FS-TL formulation over conventional approaches in skin cancer management.