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

Abstract

Abstract 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. Graphical abstract

Keywords

• Niosomes
• Rhodamine B
• Confocal microscopy
• B16-F10 cell lines
• Penetration study