Topical buparvaquone nano-enabled hydrogels for cutaneous leishmaniasis

Area of Science:

• Pharmaceutical Sciences
• Parasitology
• Dermatology

Background:

• Leishmaniasis is a neglected tropical disease with significant global impact, particularly affecting low-income populations.
• Current treatments for cutaneous leishmaniasis (CL) are invasive, prolonged, costly, and require hospitalization, highlighting an unmet medical need.
• Buparvaquone (BPQ), a hydroxynapthoquinone, shows potential for treating CL, but requires effective drug delivery systems.

Purpose of the Study:

• To develop and optimize topical self-nanoemulsifying drug delivery systems (SNEDDS) loaded with buparvaquone (BPQ) for treating New World cutaneous leishmaniasis (CL).
• To evaluate the in vitro and in vivo efficacy of BPQ-SNEDDS hydrogels as a non-invasive therapeutic option for CL.

Main Methods:

• Development of optimized topical BPQ-SNEDDS hydrogels.
• In vivo efficacy studies in a Leishmania amazonensis BALB/c mouse model, comparing BPQ-SNEDDS gels with intralesional Glucantime®.
• Ex vivo skin permeability and in vivo tape stripping studies to assess drug localization and concentration.
• In vitro efficacy testing against Leishmania amastigotes and assessment of selectivity index.

Main Results:

• Topical BPQ-SNEDDS gels achieved a significant parasite load reduction (99.989%) in a CL mouse model, comparable to intralesional Glucantime®.
• Ex vivo and in vivo studies confirmed effective skin penetration and localization of BPQ within the stratum corneum and dermis.
• BPQ-SNEDDS hydrogels demonstrated nanomolar in vitro efficacy against Leishmania parasites with a high selectivity index.

Conclusions:

• Optimized topical BPQ-SNEDDS hydrogels represent a potentially effective and non-invasive treatment for cutaneous leishmaniasis.
• The developed nano-enabled formulation facilitates therapeutic drug concentrations within the skin, addressing limitations of current CL treatments.
• Further clinical investigation of BPQ-SNEDDS hydrogels is warranted for the management of CL.