Size-dependent effects of niosomes on the penetration of methotrexate in skin layers.

Background: Niosomes hold promise as drug delivery systems for cancer treatment, with niosome size impacting stability, biodistribution, and effectiveness. This study optimized methotrexate (MTX)-loaded niosome formulation by studying the effects of components and processing conditions on size. The niosomes formulation was made by the thin-film hydration technique. Results: The optimized formulation (NIO 17) with a 6:2:2 ratio of span 60, soya PC, and cholesterol achieved 55.05% methotrexate encapsulation, particle size 597.2 nm, PDI 0.49, and zeta potential − 23.3 mV. The compatibility of methotrexate with lipids was confirmed via Fourier transform infrared spectroscopy, and transmission electron microscopy revealed spherical, well-dispersed vesicles. Differential scanning calorimetry indicated methotrexate conversion or entrapment within vesicles. In vitro release exhibited a sustained pattern with an initial burst. NIO 17 showed potent anti-cancer activity against B16-F10 cells (GI50: 38.7176 μg/mL). Ex vivo studies suggest tailoring niosome size (597.2–982.3 nm) to target specific skin depths (0–38 μm) for enhanced localized drug delivery. Conclusions: This study demonstrates the potential of methotrexate-loaded niosomes as a novel cancer therapy approach, highlighting the potent anti-cancer activity and transdermal delivery potential of NIO 17. Further research is necessary to explore its clinical translation. [ABSTRACT FROM AUTHOR]