Microneedle-based injection of Fungizone/Amphotericin B: an effective treatment for American cutaneous leishmaniasis in mice

Amphotericin B (AmB) is a potent, accessible, FDA-approved drug against CL with damaging side effects. While newer lipid formulations have less toxicity, limitations include affordability and cold-chain requirements. CL affects mostly impoverished communities, which complicates travel to urban hospitals for treatment. Therefore, an off-clinic drug delivery system is desirable. Microneedles can deliver AmB directly to localized CL lesions, which we hypothesized would limit parasite growth without systemic toxicity. Thus, a three-by-three array of 1 mm tall stainless steel hollow microneedles was evaluated in this study. To test their efficacy, we utilized Leishmania mexicana-infected mice to model American CL. Following 20- and 10-consecutive day microneedle treatments (n = 5/group), the 20-day trials more strongly limited lesion growth by up to 2.8 mm versus a maximum 1.1 mm difference between the drug and placebo groups in the 10-day trial (p = 0.008, p = 0.075, respectively). Also, treatments were associated with reduced parasitic burden weeks after treatment cessation, as assessed by limiting dilution (p = 0.057 for 10-day, p = 0.075 for 20-day; one-tailed Mann‒Whitney U test). No elevation of blood serum creatinine or blood urea nitrogen levels was observed, supporting the hypothesis of lessened kidney toxicity. Additionally, flow cytometry explorations showed differences in IL-17 and IFN-γ positivity, and histological changes were observed in the upper dermis. These promising results represent the first test of hollow microneedles for CL treatment and pave the way for further trials. The adoption of microneedles could reduce CL burden in affected communities because of their ease of use, efficacy, and safety with a pre-approved drug.