Drug Delivery Investigation of Trans-Ferulic Acid Loaded Proniosomal Gels.

BACKGROUND: Proniosomes are anhydrous, free-flowing formulations that, upon hydration, yield niosomes-lipid-based vesicles. These biocompatible vesicles represent a promising vehicle for drug delivery in melanoma treatment. METHODS: This study aimed to develop a melanoma therapy by combining the benefits of proniosomes with the reported anticancer activity of the natural phenolic compound Trans-ferulic acid (T-FA). Six formulations of T-FA-loaded-proniosomes (PrN-1 to PrN-6) were prepared and compared in terms of their physicochemical parameters, entrapment efficiency, and antioxidant activity. Additionally, cytotoxicity against melonoma cells and skin permeability of the proniosome-loaded-T-FA formulations were studied. RESULTS: The optimized T-FA niosomal dispersions showed a %EE of 69.01%, zeta potential of 37.6 mV, PDI of 0.237, %TLC of 34.51%, and nanosized particles. The hydrated niosomal dispersions preserved the scavenging capacity of T-FA (SC50 of 11.34-12.17 μg/mL). The T-FA- niosomal dispersions for PrN-1 (IC50 of 171.75 μg/mL) and PrN-5 (IC50 of 41.58 μg/mL) exhibited greater cytotoxicity on the A-375 melanoma cell line compared to free T-FA (IC50 of 275.06 μg/mL). The in vitro release study showed a pH-sensitive and diffusion-based sustained release behavior. The permeability of T-FA from the proniosomal gel displayed optimum permeability coefficient and T-FA flux; PrN-2 (0.00379 ± 0.0006 cm/h and 7.586 ± 0.11 μg/cm2 h-1) and PrN-5 (0.00434 ± 0.001 cm/h and 8.69 ± 0.13 μg/cm2 h-1). CONCLUSION: The prepared proniosomal gels efficiently encapsulated T-FA, maintained its antioxidant properties, and enhanced its cytotoxic effects against A-375 melanoma cells.