Experimental evaluation of the therapeutic effect of niosomal miltefosine delivered via Polyvinylpyrrolidone - hyaluronic acid microneedle patches against Leishmania major.

Cutaneous leishmaniasis (CL) is a prevalent parasitic disease endemic to tropical and subtropical regions, primarily caused by Leishmania major. Conventional treatment with anti-leishmanial drugs like miltefosine (MIL) is challenging due to poor skin penetration, systemic toxicity, and patient compliance issues. This study aimed to develop a stable niosomal MIL formulation (NMIL) and integrate it into dissolving microneedles (MNs) to enhance skin permeability and enable sustained drug release. We hypothesized that this combined strategy would reduce systemic toxicity and achieve more effective localized CL treatment. The optimized NMIL demonstrated nanoscale size, high stability, and efficient drug encapsulation. NMIL showed superior antileishmanial activity against both promastigote and amastigote forms compared with free MIL. Moreover, MNs loaded with NMIL exhibited sufficient mechanical strength for skin penetration and facilitated deep dermal delivery. In a murine model, the NMIL-MN combination significantly reduced lesion sizes relative to controls. In conclusion, this study demonstrates a novel niosome-MN approach that effectively addresses MIL delivery challenges by combining stability, sustained release, and deep skin penetration for improved CL therapy.