Lymphatic-targeted amphotericin B nanocrystals delivered using microarray patches applied to cutaneous leishmaniasis

Area of Science:

• Pharmaceutical Sciences
• Parasitology
• Biomaterials Engineering

Background:

• Leishmaniasis is a neglected tropical disease affecting impoverished populations, with cutaneous leishmaniasis (CL) being the most common form.
• Current treatments like Amphotericin B (AmB) face challenges due to toxicity and administration route, particularly in resource-limited settings.
• Effective delivery to lymphatic system targets Leishmania parasites but is hindered by conventional methods.

Purpose of the Study:

• To develop and evaluate intradermal delivery of Amphotericin B nanocrystals (AmB-NCs) using dissolving microarray patches (MAPs) for enhanced lymphatic targeting.
• To assess the in vitro, ex vivo, and in vivo performance of AmB-NCs MAPs compared to conventional AmB formulations.
• To investigate the potential of AmB-NCs MAPs as a minimally invasive and effective treatment for cutaneous leishmaniasis.

Main Methods:

• Amphotericin B nanocrystals (AmB-NCs) were formulated via media milling to a particle size of ~108 nm.
• In vitro studies assessed dissolution, antileishmanial activity, and host cell toxicity.
• Ex vivo and in vivo studies utilized rat models to evaluate intradermal drug deposition and lymphatic accumulation after MAP application versus intravenous administration.

Main Results:

• AmB-NCs demonstrated faster dissolution, potent antileishmanial activity, and reduced host cell toxicity in vitro.
• MAPs achieved significant intradermal drug deposition.
• In vivo studies showed 3.2-fold and 2.8-fold higher AmB accumulation in target lymph nodes with MAPs compared to IV AmBisome®, with reduced accumulation in other organs.

Conclusions:

• AmB-NCs delivered via dissolving MAPs offer a promising, minimally invasive strategy for cutaneous leishmaniasis treatment.
• This novel approach enhances lymphatic drug targeting, potentially improving therapeutic outcomes.
• AmB-NCs MAPs address key treatment barriers, offering a viable alternative for resource-limited settings.