Microneedle-Based Delivery of Amphotericin B for Treatment of Cutaneous Leishmaniasis
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Current therapeutic options against cutaneous leishmaniasis are plagued by several weaknesses. The effective topical delivery of an antileishmanial drug would be useful in treating some forms of cutaneous leishmaniasis. Toward this end, a microneedle based delivery approach for the antileishmanial drug amphotericin B was investigated in murine models of both New World (Leishmania mexicana) and Old World (Leishmania major) infection. In the L. mexicana model, ten days of treatment began on day 35 post infection, when the area of nodules averaged 9–15 mm2. By the end of the experiment, a significant difference in nodule area was observed for all groups receiving topical amphotericin B at 25 mg/kg/day after application of microneedle arrays of 500, 750, and 1000 μM in nominal length compared to the group that received this dose of topical amphotericin B alone. In the L. major model, ten days of treatment began on day 21 post infection when nodule area averaged 51–65 mm2 in the groups. By the end of the experiment, there was no difference in nodule area between the group receiving 25 mg/kg of topical amphotericin B after microneedle application and any of the non-AmBisome groups. These results show the promise of topical delivery of amphotericin B via microneedles in treating relatively small nodules caused by L. mexicana. These data also show the limitations of the approach against a disseminated L. major infection. Further optimization of microneedle delivery is needed to fully exploit this strategy for cutaneous leishmaniasis treatment.
KeywordsMicroneedle Drug delivery Amphotericin B Leishmaniasis
The authors would like to acknowledge support from the National Institutes of Health (R21 AI117748 02). We thank Abhay Satoskar and Chad Rappleye for helpful discussions and Ben Russell for assistance with the animal studies and for authenticating the Leishmania parasites. We thank Chuck Mooney and the Analytical Instrumentation Facility for assistance with scanning electron microscopy and energy dispersive X-ray spectroscopy.
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