Laboratório de Desenvolvimento Galênico (LADEG), Departamento de Fármacos e Medicamentos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Laboratório de Farmacotécnica Experimental, Instituto de Tecnologia em Fármacos - Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
Drug Deliv Transl Res. 2020 Dec;10(6):1552-1570. doi: 10.1007/s13346-020-00821-5.
Leishmaniasis is a neglected infectious disease caused by protozoan parasites from Leishmania genus species, affecting millions of people, in several countries. The current available treatment for cutaneous leishmaniasis (CL) has presented many side effects. In this way, micro- and nanotechnology are important processes, since they may be useful for release profile modulation of CL drugs improving their bioavailability. Amphotericin B (AmB) is a macrolide antibiotic used as a second-choice treatment. This study aimed the development of oil-water nanoemulsions (NEs) containing AmB for topical administration to treat CL. Furthermore, NEs were characterized by their droplet size, morphology, drug content, stability, in vitro release profile, and ex vivo skin permeation. In vitro anti-leishmanial activity using Leishmania amazonensis promastigotes was also evaluated. NEs containing AmB presented droplet size lower than 60 nm with a polydispersity index lower than 0.5. The best AmB-NEs were submitted to stability tests and these formulations presented excellent results after 365 days under refrigeration, confirming the maintenance of the drug content higher than 95%. AmB-NEs displayed slow and controlled AmB kinetic release and low skin permeation. These formulations presented lower cytotoxicity in comparison with free AmB and higher anti-leishmanial effect against L. amazonensis promastigotes. Therefore, the selected AmB-NE formulations, especially AmB-NE01, presented promising results as novel alternatives for CL treatment. Graphical abstract.
利什曼病是一种由利什曼原虫属种的原生动物寄生虫引起的被忽视的传染病，影响了多个国家的数百万人。目前可用于治疗皮肤利什曼病（CL）的方法存在许多副作用。在这种情况下，微纳米技术是重要的过程，因为它们可能有助于调节 CL 药物的释放特性，提高其生物利用度。两性霉素 B（AmB）是一种大环内酯类抗生素，用作二线治疗药物。本研究旨在开发含有 AmB 的油包水纳米乳剂（NE），用于局部治疗 CL。此外，还对 NE 的粒径、形态、药物含量、稳定性、体外释放特性和体外皮肤渗透进行了表征。还评估了使用利什曼原虫前鞭毛体进行的体外抗利什曼活性。含有 AmB 的 NE 的粒径小于 60nm，多分散指数低于 0.5。最佳的 AmB-NE 制剂进行了稳定性测试，这些制剂在冷藏 365 天后仍具有出色的结果，证实药物含量保持在 95%以上。AmB-NE 显示出缓慢和受控的 AmB 动力学释放以及低皮肤渗透。与游离 AmB 相比，这些制剂的细胞毒性较低，对利什曼原虫前鞭毛体的抗利什曼效果更高。因此，所选的 AmB-NE 制剂，特别是 AmB-NE01，作为 CL 治疗的新选择具有很大的潜力。
