Enhanced Topical Delivery of Methotrexate via Transferosome-Loaded Microneedle Array Patch: Formulation, Optimization, and In Vitro–In Vivo Assessment

<b>Background:</b> Conventional approaches in treating psoriasis demonstrate several complications. methotrexate (MTX) has been frequently used for its efficacy in managing moderate to severe psoriasis. However, MTX acts as an antagonist in regular dosage, which creates a patient compliance issue with undesirable consequences for patients, which necessitates development of an innovative approach to enhance skin permeation. Therefore, this study examines the improved topical administration of MTX utilizing a transferosome-loaded microneedle (MNs) array patch for the management of psoriasis. <b>Methods:</b> A design of experiment was used assess the effect of phospholipid content and edge activator type on vesicle size and entrapment efficiency (EE) to fabricate and optimize transferosome-loaded MTX. Furthermore, the MTX was incorporated within MNs and assessed for in vitro-ex vivo-in vivo parameters. <b>Results:</b> The morphology result revealed vesicles mean diameter of 169.4 ± 0.40 nm and EE of 69 ± 0.48 (%). Compared to traditional formulations (MTX patch and gel), the optimized transferosome-loaded dissolving MN array patch showed a substantial increase in diffusion of MTX tested over rat skin. Furthermore, an enhanced therapeutic benefit at the application site through cumulative drug release profiles suggested sustained release of MTX over 24 h. Moreover, in vivo experiments showed that the MN array patch exhibited higher accumulation, compared to conventional formulation tested. In addition, the plasma concentration measurements demonstrated a reduction in systemic exposure to MTX, diminishing the possibility of intricacy while preserving localized therapeutic efficacy. The capability of the MN array patch to lance the epidermal layers was proven by histological assessments. <b>Conclusions:</b> Thus, transferosome-loaded MNs is a viable method of delivering MTX topically with prolonged drug release and reduced systemic toxicity.