Lipid-Based Nanocarriers for Topical Therapy of Cutaneous Leishmaniasis: An Insight into the Mechanism of Action

Abstract

Cutaneous leishmaniasis (CL) is a parasitic infection caused by Leishmania species, affecting millions worldwide. The current treatment options for CL have several limitations, including low efficacy, inability to reach the target site, potential toxicity, and longer treatment duration, leading to poor patient compliance. Therefore, there is an urgent need for alternative treatments, especially topical ones, that are more effective, safe, and patient-friendly. Although numerous reviews have described the advantages of a wide range of nanoparticles in the treatment of CL, this review narrows its focus to the utilization of novel lipid-based nanocarriers for the topical treatment of CL, offering an in-depth analysis of the topical potential and mechanism of skin permeation of these lipidic nanocarriers. Lipid-based nanostructures such as liposomes, solid lipid nanoparticles, and nanostructured lipid carriers have been extensively studied for CL treatment, either alone or in combination with other drugs or therapies. These carriers can improve the bioavailability, stability, and efficacy of the drug, target the infected site, and reduce adverse effects on healthy tissues. Moreover, these can be easily formulated into different dosage forms, such as creams, gels, or ointments, for convenient topical application. Despite the many benefits of lipid-based carriers, there are still some challenges that need to be addressed, such as optimizing the formulation parameters, ensuring the reproducibility and scalability of the process, and evaluating the long-term safety and efficacy in clinical trials. This study aims to provide a comprehensive overview of the current state-of-the-art lipid-based nanocarriers for topical treatment of CL, covering the recent advances, limitations, clinical evidence, and prospects of this promising approach. In addition, the skin and macrophage targeting potential of various lipid-based nanocarriers is also discussed, which is especially helpful in treating the lesions of CL.

1

Life cycle of Leishmania parasites (created in BioRender; Muqaddas, H. (2025) https://BioRender.com/yh568bs).

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Various skin changes may occur during the course of the disease of CL. (A) Intact skin was treated with stratum corneum, viable epidermis, and dermis. (B) Lesion characterized by partial damage to the skin, stratum corneum barrier function is lost, and dermis filled with infected macrophages. (C) Ulcerative lesion characterized by loss of stratum corneum and epidermis, fewer macrophages, and increased inflammatory mediators (created in BioRender; Riaz, A. (2025) https://BioRender.com/in2fttn).

3

Lipid nanocarriers targeting dermis and macrophages (created in BioRender; Riaz, A. (2025) https://BioRender.com/r5f7vf8).

4

Liposome: lipid bilayer enclosing an aqueous shell. Transferosome: phospholipid nanocarrier containing single-chain surfactant inside the lipid bilayer, as edge activator. Ethosome: ethanol containing phospholipid nanocarrier. The globule of nanoemulsion: o/w type, oil globule stabilized by surfactant molecules. Solid lipid nanoparticle (SLN): solid lipid globule surrounded and stabilized by surfactant molecules. Nanostructured lipid carrier (NLC): globule consisting of a blend of solid and liquid lipid surrounded by surfactant molecules (created in BioRender; KHAN, M. (2025) https://BioRender.com/umarxxb).

5

Structure of liposomes, transferosomes, and ethosomes (left) and skin permeation mechanism for ultradeformable liposomes (right) (created in BioRender; Riaz, A. (2025) https://BioRender.com/t63tl3h).