Department of Pharmacy, Faculty of Biological Sciences, Quaid-e-Azam University, Islamabad, Pakistan.
Department of Nanosciences & Technology, National Centre for Physics, Quaid-e-Azam University, Islamabad, Pakistan.
Drug Dev Ind Pharm. 2021 Mar;47(3):440-453. doi: 10.1080/03639045.2021.1890768. Epub 2021 Mar 1.
The purpose of this study was to develop novel carbopol-based miltefosine-loaded transfersomal gel (HePCTG) for the treatment of cutaneous leishmaniasis (CL) efficient targeting of leishmania infected macrophages.
Miltefosine-loaded transfersomes (HePCT) were prepared by ethanol injection method followed by their incorporation into carbopol gel to form HePCTG. The prepared HePCT were assessed for physicochemical properties including mean particle size, polydispersity index, zeta potential, entrapment efficiency, morphology, and deformability. Similarly, HePCTG was evaluated for physiochemical and rheological attributes. The release, skin permeation, skin irritation, anti-leishmanial activity, and efficacy in mice against infected macrophages were also performed for HePCT.
The optimized HePCT displayed a particle size of 168 nm with entrapment efficiency of 92%. HePCTG showed suitable viscosity, pH, and sustained release of the incorporated drug. Furthermore, HePCT and HePCTG demonstrated higher skin permeation than drug solution. The results of macrophage uptake study indicated improved drug intake by passive diffusion. The lower half maximal inhibitory concentration value, selectivity index and higher 50% cytotoxic concentration value of HePCT compared to that of HePC solution demonstrated the improved anti-leishmanial efficacy and non-toxicity of the formulation. This was further confirmed by the notable reduction in parasite load and lesion size observed in anti-leishmanial study.
It can be stated that the formulated HePCTG can effectively be used for the treatment of CL.
本研究旨在开发新型卡波姆载米替福新传递体凝胶（HePCTG），用于治疗皮肤利什曼病（CL），以有效靶向感染巨噬细胞的利什曼原虫。
采用乙醇注入法制备米替福新传递体（HePCT），再将其掺入卡波姆凝胶中形成 HePCTG。对制备的 HePCT 进行理化性质评估，包括平均粒径、多分散指数、Zeta 电位、包封效率、形态和变形性。同样，对 HePCTG 进行理化和流变特性评估。还对 HePCT 的释放、皮肤渗透、皮肤刺激性、抗利什曼原虫活性和对感染巨噬细胞的疗效进行了评价。
优化的 HePCT 显示粒径为 168nm，包封效率为 92%。HePCTG 表现出适宜的粘度、pH 值和所载药物的持续释放。此外，HePCT 和 HePCTG 显示出比药物溶液更高的皮肤渗透。巨噬细胞摄取研究的结果表明，药物通过被动扩散摄入增加。与 HePC 溶液相比，HePCT 的半数最大抑制浓度值、选择性指数和更高的 50%细胞毒性浓度值表明该制剂具有更好的抗利什曼原虫效果和非毒性。这在抗利什曼原虫研究中观察到寄生虫负荷和病变大小的显著减少中得到了进一步证实。
可以说，所构建的 HePCTG 可有效用于治疗 CL。
