Institute of Tropical Health, Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain.
ACS Infect Dis. 2021 Dec 10;7(12):3197-3209. doi: 10.1021/acsinfecdis.1c00394. Epub 2021 Nov 12.
Leishmaniasis urgently needs new oral treatments, as it is one of the most important neglected tropical diseases that affects people with poor resources. The drug discovery pipeline for oral administration currently discards entities with poor aqueous solubility and permeability (class IV compounds in the Biopharmaceutical Classification System, BCS) such as the diselenide , a trypanothione reductase (TR) inhibitor. This work was assisted by glyceryl palmitostearate and diethylene glycol monoethyl ether-based nanostructured lipid carriers (NLC) to render bioavailable and effective after its oral administration. The loading of in NLC drastically enhanced its intestinal permeability and provided plasmatic levels higher than its effective concentration (IC). In infected BALB/c mice, -NLC reduced the parasite burden in the spleen, liver, and bone marrow by at least 95% after 5 doses, demonstrating similar efficacy as intravenous Fungizone. Overall, compound and its formulation merit further investigation as an oral treatment for visceral leishmaniasis.
利什曼病迫切需要新的口服治疗方法，因为它是影响资源匮乏人群的最重要的被忽视热带病之一。目前，口服给药的药物发现管道会淘汰水溶性和渗透性差的实体（生物药剂学分类系统中的 IV 类化合物），如二硒化物，一种硫氧还蛋白还原酶 (TR) 抑制剂。这项工作得到了甘油棕榈酸硬脂酸酯和二乙二醇单乙基醚基纳米结构化脂质载体 (NLC) 的辅助，使其在口服后具有生物利用度和有效性。在 NLC 中负载 可显著提高其肠道通透性，并提供高于有效浓度 (IC) 的血浆水平。在感染的 BALB/c 小鼠中，-NLC 在 5 次给药后可使脾脏、肝脏和骨髓中的寄生虫负荷减少至少 95%，其疗效与静脉注射两性霉素 B 相当。总的来说，化合物 和其制剂有理由作为一种治疗内脏利什曼病的口服药物进行进一步研究。
