Cutaneous leishmaniasis (CL) remains a neglected tropical disease with significant psychosocial and economic impacts, primarily affecting resource-limited regions.
Current chemotherapies, including pentavalent antimonials, amphotericin B, and miltefosine, are plagued by systemic toxicity, poor bioavailability, emerging drug resistance, and inadequate targeting of intracellular Leishmania amastigotes within macrophages. Nanomedicine has emerged as a new strategy to overcome these limitations by repurposing existing drugs through advanced delivery systems. This review comprehensively examined the application of various nanocarrier platforms, including liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), polymeric nanoparticles, and metallic nanoparticles for the treatment of CL. These systems function by leveraging passive targeting via the enhanced permeability and retention (EPR) effect at lesion sites and active targeting through innate macrophage phagocytosis.
Key advantages include enhanced drug solubility, prolonged circulation, improved bioavailability, reduced systemic toxicity, and increased intracellular drug accumulation. The clinical success of liposomal amphotericin (AmBisome®) exemplifies the potential of nanomedicine, offering high efficacy with minimal nephrotoxicity. Topical applications of SLNs/NLCs show promise for non-invasive treatment, while polymeric and metallic nanoparticles enable controlled release and multimodal therapy.
Despite these advancements, challenges related to scalability, regulatory approval, long-term stability, and affordability in endemic regions remain. Future directions include the development of ligand-functionalized “smart” nanoparticles, combination therapies, and plant-based nanoformulations. Nanomedicine represents a paradigm shift in CL treatment, bridging the gap between drug efficacy and clinical applicability through precision targeting and enhanced therapeutic outcomes.