Department of Pharmacy, Federal University of Sergipe, São Cristóvão, SE, Brazil.
Center for Research in Medicinal Plants, Federal University of Piauí, Teresina, PI, Brazil.
Exp Parasitol. 2024 Oct;265:108808. doi: 10.1016/j.exppara.2024.108808. Epub 2024 Jul 31.
This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.
本研究旨在开发含有 α- 姜烯醇的微乳（MEs），用于治疗皮肤利什曼病（CL）。首先，使用 α- 姜烯醇作为油相、Eumulgin® CO 40 作为表面活性剂、Polymol® HE 作为助表面活性剂、蒸馏水作为水相，制备伪三元相图。选择并表征了两个含有 5%α- 姜烯醇的透明液体系统（TLS）（F5E25 和 F5EP25）。接下来，使用 Franz 细胞进行皮肤渗透和保留实验。使用傅里叶变换红外光谱（FTIR）技术评估制剂与角质层（SC）的相互作用。在鼠腹腔巨噬细胞中评估细胞毒性。最后，在 L. amazonensis（MHOM/BR/77/LTB 0016 株）的前鞭毛体和无鞭毛体中测定微乳的抗利什曼原虫活性。结果表明，所选配方具有各向同性、纳米尺寸（低于 25nm）、牛顿行为和 pH 值在 6.5 至 6.9 之间。MEs 使 α- 姜烯醇的通量和透皮量增加了 2.5 倍。ATR-FTIR 结果表明，微乳促进了角质层的脂质和蛋白质的流态化和提取，增加了药物在皮肤中的扩散系数和分配系数。此外，与未包裹的 α- 姜烯醇（IC 53.8）相比，F5E25 和 F5EP25 对前鞭毛体的活性更高（IC 13.27 和 18.29）。此外，F5E25 和 F5EP25 对 L. amazonensis 内阿米巴原虫也具有抗利什曼原虫活性，其 IC 50 低于游离 α- 姜烯醇，且选择性指数高（高达 15）。因此，所获得的系统有利于局部给药，对 L. amazonensis 前鞭毛体和无鞭毛体具有显著的抗利什曼原虫活性，是未来体内试验的有前途的系统。
