Macrophage targeting with the novel carbopol-based miltefosine-loaded transfersomal gel for the treatment of cutaneous leishmaniasis: in vitro and in vivo analyses

• Published in: Drug development and industrial pharmacy 2021-03, Vol.47 (3), p.440-453
• Main Authors: Batool, Sibgha, Zahid, Fatima, Ud-Din, Fakhar, Naz, Syeda Sohaila, Dar, Muhammad Junaid, Khan, Muhammad Waseem, Zeb, Alam, Khan, Gul Majid
• Format: Article
• Language: English
• Subjects: Acrylic Resins; Animals; ethanol injection method; leishmaniasis; Leishmaniasis, Cutaneous - drug therapy; macrophage targeting; Macrophages; Mice; Mice, Inbred BALB C; Miltefosine; Phosphorylcholine - analogs & derivatives; transfersomes
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639045.2021.1890768

The purpose of this study was to develop novel carbopol-based miltefosine-loaded transfersomal gel (HePCTG) for the treatment of cutaneous leishmaniasis (CL) via 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 in vitro release, skin permeation, skin irritation, anti-leishmanial activity, and in vivo efficacy in BALB/c 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 in vivo anti-leishmanial study. It can be stated that the formulated HePCTG can effectively be used for the treatment of CL.