Departamento de Fisiologia e Biofísica, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
Biomed Pharmacother. 2021 Feb;134:111120. doi: 10.1016/j.biopha.2020.111120. Epub 2020 Dec 17.
Visceral leishmaniasis (VL) is a systemic parasitic disease that leads to high rates of morbidity and mortality in humans worldwide. There is a great need to develop new drugs and novel strategies to make chemotherapy for this disease more efficacious and well tolerated. Recent reports on the immunomodulatory effects and the low toxicity of the spherical carbon nanostructure fullerol led us to investigate in vitro and in vivo antileishmanial activity in free and encapsulated forms in liposomes. When assayed against intramacrophagic Leishmania amastigotes, fullerol showed a dose-dependent reduction of the infection index with IC of 0.042 mg/mL. When given daily by i.p. route for 20 days (0.05 mg/kg/d) in a murine model of acute VL, fullerol promoted significant reduction in the liver parasite load. To improve the delivery of fullerol to the infection sites, liposomal formulations were prepared by the dehydration-rehydration method. When evaluated in the acute VL model, liposomal fullerol (Lip-Ful) formulations given i.p. at 0.05 and 0.2 mg/kg with 4-days intervals were more effective than the free form, with significant parasite reductions in both liver and spleen. Lip-Ful at 0.2 mg/kg promoted complete parasite elimination in the liver. The antileishmanial activity of Lip-Ful was further confirmed in a chronic model of VL. Lip-Ful was also found to induce secretion of pro-inflammatory TNF-α, IFN-γ and IL-1β cytokines. In conclusion, this work reports for the first time the antileishmanial activity of fullerol and introduces an innovative approach for treatment of VL based on the association of this nanostructure with liposomes.
内脏利什曼病（VL）是一种全身性寄生虫病，在全球范围内导致高发病率和死亡率。因此，非常有必要开发新的药物和新的策略，以使这种疾病的化疗更有效和耐受良好。最近有关球形碳纳米结构富勒烯的免疫调节作用和低毒性的报告促使我们研究游离形式和脂质体包封形式的富勒烯在体外和体内的抗利什曼原虫活性。当检测针对巨噬细胞内利什曼原虫无鞭毛体时，富勒烯显示出剂量依赖性的感染指数降低，IC 为 0.042mg/mL。当在急性 VL 小鼠模型中通过腹腔内途径每天给予 20 天（0.05mg/kg/d）时，富勒烯促进了肝寄生虫负荷的显著降低。为了提高富勒烯向感染部位的递送，通过脱水-再水化法制备了脂质体制剂。当在急性 VL 模型中进行评估时，在 4 天的间隔时间内以 0.05 和 0.2mg/kg 的剂量通过腹腔内给予的脂质体富勒烯（Lip-Ful）制剂比游离形式更有效，在肝和脾中均有显著的寄生虫减少。Lip-Ful 以 0.2mg/kg 剂量可促进肝内寄生虫的完全消除。Lip-Ful 在慢性 VL 模型中的抗利什曼原虫活性也得到了进一步证实。还发现 Lip-Ful 诱导促炎 TNF-α、IFN-γ和 IL-1β细胞因子的分泌。总之，这项工作首次报道了富勒烯的抗利什曼原虫活性，并引入了一种基于将这种纳米结构与脂质体结合的治疗 VL 的创新方法。
