Department of Biological Sciences and Health, Amapá Federal University, Macapá, Amapá, Brazil.
Department of Clinical and Toxicological Analyses, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Biomed Pharmacother. 2021 Feb;134:111109. doi: 10.1016/j.biopha.2020.111109. Epub 2020 Dec 16.
Cutaneous leishmaniasis (CL) is a neglected tropical skin disease caused by the protozoan genus Leishmania. The treatment is restricted to a handful number of drugs that exhibit toxic effects, limited efficacy, and drug resistance. Additionally, developing an effective topical treatment is still an enormous unmet medical challenge. Natural oils, e.g. the oleoresin from P. emarginatus fruits (SO), contain various bioactive molecules, especially terpenoid compounds such as diterpenes and sesquiterpenes. However, its use in topical formulations can be impaired due to the natural barrier of the skin for low water solubility compounds. Nanoemulsions (NE) are drug delivery systems able to increase penetration of lipophilic compounds throughout the skin, improving their topical effect. In this context, we propose the use of SO-containing NE (SO-NE) for CL treatment. The SO-NE was produced by a low energy method and presented suitable physicochemical characteristic: average diameter and polydispersity index lower than 180 nm and 0.2, respectively. Leishmania (Leishmania) amazonensis-infected BALB/c mice were given topical doses of SO or SO-NE. The topical use of a combination of SO-NE and intraperitoneal meglumine antimoniate reduced lesion size by 41 % and tissue regeneration was proven by histopathological analyses. In addition, a reduction in the parasitic load and decreased in the level of IFN-γ in the lesion may be associated, as well as a lower level of the cytokine IL-10 may be associated with a less intense inflammatory process. The present study suggests that SO-NE in combination meglumine antimoniate represents a promising alternative for the topical treatment of CL caused by L. (L.) amazonensis.
皮肤利什曼病(CL)是一种被忽视的热带皮肤疾病,由原生动物属利什曼原虫引起。治疗方法仅限于少数几种具有毒性作用、疗效有限和耐药性的药物。此外,开发有效的局部治疗仍然是一个巨大的未满足的医学挑战。天然油,例如 P. emarginatus 果实的油树脂(SO),含有各种生物活性分子,特别是萜类化合物,如二萜和倍半萜。然而,由于皮肤的天然屏障对低水溶性化合物的阻碍,其在局部制剂中的应用受到限制。纳米乳剂(NE)是一种药物传递系统,能够增加亲脂性化合物在整个皮肤中的渗透,从而提高其局部效果。在这种情况下,我们提出使用含有 SO 的 NE(SO-NE)来治疗 CL。SO-NE 通过低能量方法制备,具有合适的物理化学特性:平均直径和多分散指数分别低于 180nm 和 0.2。对感染了 Leishmania(Leishmania) amazonensis 的 BALB/c 小鼠给予 SO 或 SO-NE 的局部剂量。SO-NE 与腹腔内葡萄糖酸锑钠联合使用可使病变面积减少 41%,并通过组织病理学分析证明组织再生。此外,病变中寄生虫载量的减少和 IFN-γ 水平的降低可能与炎症过程不太强烈有关,而细胞因子 IL-10 水平的降低可能与炎症过程不太强烈有关。本研究表明,SO-NE 联合葡萄糖酸锑钠可能是治疗由 L.(L.) amazonensis 引起的 CL 的一种有前途的局部替代疗法。