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Nitric-oxide releasing chitosan nanoparticles towards effective treatment of cutaneous leishmaniasis
Nitric Oxide ( IF 3.2 ) Pub Date : 2021-05-01 , DOI: 10.1016/j.niox.2021.04.008
Fernanda V Cabral 1 , Milena T Pelegrino 2 , Amedea B Seabra 2 , Martha S Ribeiro 1
Affiliation  

Cutaneous leishmaniasis (CL) is a major public health problem caused by Leishmania parasites that produce destructive and disfiguring skin conditions. There is an urgent need for alternative topical therapies due to the limitations of current systemic treatments. Recently, we have synthesized nitric oxide-releasing chitosan nanoparticles (NONPs) and shown their potential in vitro against Leishmania amazonensis. Herein we evaluated the application of NONPs for the treatment of CL on infected BALB/c mice. Mice were treated with topical administration of increasing concentrations of NONPs and disease progression was investigated regarding parasite load, lesion thickness, and pain score. As a result, we observed a dose-dependent NONPs effect. Parasite burden and lesion thickness were substantially lower on animals receiving NONPs at a 2 mM concentration compared to untreated control. Moreover, the clinical presentation of the lesions did not show any visible signs of ulcer, suggesting clinical healing in these animals. This successful outcome was sustained for at least 21 days after therapy even in one single dose. Thus, we demonstrate that NONPs are suitable for topical administration, and represent an attractive approach to treat CL.



中文翻译:

一氧化氮释放壳聚糖纳米粒对皮肤利什曼病的有效治疗

皮肤利什曼病 (CL) 是由利什曼原虫引起的主要公共卫生问题,会产生破坏性和毁容性皮肤状况。由于当前全身治疗的局限性,迫切需要替代的局部治疗。最近,我们合成了释放一氧化氮的壳聚糖纳米粒子 (NONPs),并在体外显示了它们对抗亚马逊利什曼原虫的潜力. 在此,我们评估了 NONPs 在感染 BALB/c 小鼠上治疗 CL 的应用。用增加浓度的NONPs的局部给药对小鼠进行治疗,并就寄生虫负荷、病变厚度和疼痛评分研究疾病进展。结果,我们观察到了剂量依赖性的 NONPs 效应。与未处理的对照相比,接受 2 mM 浓度的 NONP 的动物的寄生虫负荷和病变厚度显着降低。此外,病变的临床表现没有显示任何可见的溃疡迹象,表明这些动物的临床愈合。即使是单次给药,这种成功的结果在治疗后至少持续 21 天。因此,我们证明了 NONPs 适用于局部给药,并代表了一种治疗 CL 的有吸引力的方法。

更新日期:2021-05-09
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