Institute for Technological Research of São Paulo State - Group for BioNanoManufacturing - Av. Prof. Almeida Prado, 532 - Cidade Universitária, Butantã - São Paulo - SP - 05508-901 - Brazil.
Institute of Biomedical Sciences - University of São Paulo - Department of Parasitology - Av. Prof. Lineu Prestes, 1374 - Edifício Biomédicas II, Cidade Universitária - São Paulo - SP - 05508-000 - Brazil.
Eur J Pharm Sci. 2020 Apr 30;147:105295. doi: 10.1016/j.ejps.2020.105295. Epub 2020 Mar 5.
The leishmaniases are a group of diseases caused by protozoan parasites from Leishmania species. Effectiveness therapies for cutaneous leishmaniasis (CL), the most common form, are still needed to be developed since the available drugs such as meglumine antimoniate (MA) present severe adverse reactions. Here, we develop and characterize maltodextrin polymeric colloidal nanocarriers containing MA (PCN-MA) for topical CL treatment. PCN-MA is composed of 5 to 8% maltodextrin, 0.3% NaCl, 1% MA in 21% of water as aqueous-internal phase, containing or no 3% Kolliphor® P-188, and 10% SF1540 dispersed in a silicone-based external phase. It formed a colloidal system dispersed in silicone with high encapsulation efficiency (87% to 92%) and composite spherical-shaped particles with the smooth and regular surface within the nanosized scale, which was confirmed by scanning electron microscopy (SEM) and dynamic light scattering (DLS) analysis. Ex vivo cutaneous retention studies using pig ears skin on Franz diffusion cells revealed that the MA cutaneous retention is improved when delivered by PCN. Topical PCN-MA evaluation in murine leishmaniasis model showed similar efficacy than the intraperitoneal injection of the reference medicine (Glucantime®) regarding parasite titer reduction and superior healing activity in terms of collagen area deposition. Our results suggest that this sugar-based PCN is a promising agent for topical delivery of meglumine antimoniate.
利什曼病是一组由利什曼原虫属的原生动物寄生虫引起的疾病。由于现有的药物如葡甲胺(MA)存在严重的不良反应,仍然需要开发用于治疗皮肤利什曼病(CL)的有效疗法,CL 是最常见的形式。在这里,我们开发并表征了含有 MA 的麦芽糊精聚合胶体纳米载体(PCN-MA)用于局部 CL 治疗。PCN-MA 由 5 至 8%麦芽糊精、0.3%氯化钠、1% MA 组成,水相为 21%,包含或不包含 3%的 Kolliphor® P-188,以及 10%SF1540 分散在硅酮基外部相中。它形成了一种在硅酮中分散的胶体体系,具有高包封效率(87%至 92%)和复合球形粒子,表面光滑且规则,在纳米尺度内,这通过扫描电子显微镜(SEM)和动态光散射(DLS)分析得到证实。在 Franz 扩散细胞上使用猪耳皮肤进行的体外皮肤保留研究表明,当通过 PCN 给药时,MA 的皮肤保留得到改善。PCN-MA 在小鼠利什曼病模型中的局部评价表明,在寄生虫滴度降低方面与参考药物(Glucantime®)的疗效相当,在胶原面积沉积方面具有更好的愈合活性。我们的结果表明,这种基于糖的 PCN 是一种有前途的葡甲胺经皮给药的制剂。
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