Nguyen Alexander K, Yang Kai-Hung, Bryant Kelsey, Li Junan, Joice April C, Werbovetz Karl A, Narayan Roger J
Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Box 7115, Raleigh, NC, 27695-7115, USA.
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Biomed Microdevices. 2019 Jan 7;21(1):8. doi: 10.1007/s10544-018-0355-8.
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 mm. 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 mm 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.
目前针对皮肤利什曼病的治疗方案存在若干缺陷。抗利什曼原虫药物的有效局部递送对于治疗某些形式的皮肤利什曼病会很有用。为此，在新世界（墨西哥利什曼原虫）和旧世界（硕大利什曼原虫）感染的小鼠模型中，研究了一种基于微针的抗利什曼原虫药物两性霉素B的递送方法。在墨西哥利什曼原虫模型中，感染后第35天开始为期10天的治疗，此时结节面积平均为9 - 15毫米。到实验结束时，与仅接受该剂量局部两性霉素B的组相比，在应用标称长度为500、750和1000微摩尔的微针阵列后，所有接受25毫克/千克/天局部两性霉素B的组在结节面积上观察到显著差异。在硕大利什曼原虫模型中，感染后第21天开始为期10天的治疗，此时各组结节面积平均为51 - 65毫米。到实验结束时，在应用微针后接受25毫克/千克局部两性霉素B的组与任何非两性霉素脂质体组之间在结节面积上没有差异。这些结果表明通过微针局部递送两性霉素B在治疗由墨西哥利什曼原虫引起的相对较小的结节方面具有前景。这些数据也显示了该方法在对抗播散性硕大利什曼原虫感染方面的局限性。需要进一步优化微针递送以充分利用这种策略来治疗皮肤利什曼病。
