Center for Lasers and Applications, Nuclear and Energy Research Institute (IPEN-CNEN/SP), Av. Prof. Lineu Prestes, 2242, CEP 05508-000, São Paulo, SP, Brazil.
Center for Natural and Human Sciences, Universidade Federal do ABC, Av. dos Estados 5001, CEP 09210-580, Santo André, SP, Brazil; Nanomedicine Research Unit (NANOMED), Universidade Federal do ABC, Santo André, SP, Universidade Federal do ABC, Av. dos Estados 5001, CEP 09210-580, Santo André, SP, Brazil.
Nitric Oxide. 2019 Dec 1;93:25-33. doi: 10.1016/j.niox.2019.09.007. Epub 2019 Sep 18.
Leishmaniasis is a neglected tropical disease that demands for new therapeutic strategies due to adverse side effects and resistance development promoted by current drugs. Nitric oxide (NO)-donors show potential to kill Leishmania spp. but their use is limited because of their instability. In this work, we synthesize, characterize, and encapsulate S-nitroso-mercaptosuccinic acid into chitosan nanoparticles (NONPs) and investigate their activity on promastigotes and intracellular amastigotes of Leishmania (Leishmania) amazonensis. Cytotoxicity on macrophages was also evaluated. We verified that NONPs reduced both forms of the parasite in a single treatment. We also noticed reduction of parasitophorous vacuoles as an evidence of inhibition of parasite growth and resolution of infection. No substantial cytotoxicity was detected on macrophages. NONPs were able to provide a sustained parasite killing for both L. (L.) amazonensis infective stages with no toxicity on macrophages, representing a promising nanoplatform for cutaneous leishmaniasis.
利什曼病是一种被忽视的热带病，由于现有药物的不良反应和耐药性的发展，需要新的治疗策略。一氧化氮（NO）供体具有杀伤利什曼原虫的潜力，但由于其不稳定性，其应用受到限制。在这项工作中，我们合成、表征并将 S-亚硝基巯基丁二酸包封到壳聚糖纳米粒子（NONPs）中，并研究它们对亲脂体和内阿米巴利什曼原虫（利什曼原虫）的活性。还评估了对巨噬细胞的细胞毒性。我们验证了 NONPs 在单次治疗中减少了两种形式的寄生虫。我们还注意到寄生泡的减少，这是抑制寄生虫生长和解决感染的证据。在巨噬细胞上未检测到明显的细胞毒性。NONPs 能够为两种 L.（L.）亚马逊感染阶段提供持续的寄生虫杀伤作用，而对巨噬细胞没有毒性，这代表了一种有前途的皮肤利什曼病纳米平台。
