Advances and challenges in novel drug delivery systems for the treatment of leishmaniases: A comprehensive narrative review.

Leishmaniases, neglected tropical diseases comprising diverse clinical forms and manifestations depending upon the causative Leishmania species, remain a major public health concern globally. Broadly, the diseases are classified into cutaneous (CL), mucocutaneous (MCL) and visceral (VL) forms based on tissue invasion and pathogenesis. Conventional therapeutic agents, including antimonial compounds, amphotericin B, miltefosine, pentamidine, and paromomycin, are limited by high toxicity, emerging resistance, and poor bioavailability. Leishmania amastigotes proliferate within macrophages of the reticuloendothelial system, posing a significant challenge for effective drug delivery. Recent advancements in novel drug delivery systems (NDDS) incorporating diverse nano-formulations offer promising solutions by enhancing targeting efficiency and reducing systemic side effects. This review evaluates current literature (2000-2025) regarding NDDS applications against CL (including MCL) and VL. While formulations like AmBisome are clinically established, many others remain in preclinical stages. This paper critically analyzes the transition from conventional to novel therapies, the mechanisms of intracellular delivery, and the regulatory hurdles delaying clinical translation.