Raw_Data_Antileishmanial activity of fullerol and its liposomal formulation in experimental models of visceral leishmaniasis.xlsx

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 <i>in vitro</i> and in <i>vivo</i> its antileishmanial activity in free and encapsulated forms in liposomes. When assayed against intramacrophagic <i>Leishmania</i> amastigotes, fullerol showed a dose-dependent reduction of the infection index with IC₅₀ 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. When evaluated under the liposomal form at 0.05 and 0.2 mg/kg with 4-days intervals, it was more effective than the free form, with significant parasite reductions in both liver and spleen. Liposomal fullerol at 0.2 mg/kg promoted the complete parasite elimination in the liver and significant increase in levels of pro-inflammatory TNF-α and IFN-g. The antileishmanial activity of the liposomal fullerol was further confirmed in a chronic model of VL. 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（Visceral leishmaniasis, VL）是一种在全球范围内导致人类高发病率与高死亡率的全身性寄生虫病，当前亟需开发新型药物与治疗策略，以提升该病化疗方案的疗效与耐受性。近期有研究报道球形碳纳米结构富勒醇（fullerol）具备免疫调节活性且毒性较低，为此本团队探究了其游离形式与脂质体（liposomes）包载形式在体外（in vitro）和体内（in vivo）的抗利什曼活性。针对巨噬细胞内的利什曼原虫无鞭毛体（Leishmania amastigotes）开展实验时，富勒醇可使感染指数呈剂量依赖性降低，半数抑制浓度（IC₅₀）为0.042 mg/mL。在急性内脏利什曼病小鼠模型中，以腹腔内（i.p.）给药途径每日给药（0.05 mg/kg/d）、连续给药20天后，富勒醇可显著降低肝脏寄生虫负荷。当采用脂质体包载形式、以0.05与0.2 mg/kg剂量、每4天给药一次时，其抗利什曼活性优于游离形式，可同时显著降低肝脏与脾脏的寄生虫负荷。其中0.2 mg/kg剂量的脂质体包载富勒醇可完全清除肝脏内的寄生虫，并显著提升促炎性肿瘤坏死因子-α（TNF-α）与干扰素-γ（IFN-γ）的表达水平。脂质体包载富勒醇的抗利什曼活性在慢性内脏利什曼病模型中进一步得到验证。综上，本研究首次报道了富勒醇的抗利什曼活性，并提出了将该纳米结构与脂质体联用的创新型内脏利什曼病治疗方案。