Preparation, in-vitro and in-vivo evaluation of Rifampicin and Vancomycin Co-loaded transfersomal gel for the treatment of cutaneous leishmaniasis

Abstract

Targeted and localized drug delivery via dermal route is an effective approach to improve drug delivery and reduce drugs associated toxicities, most particularly treating cutaneous leishmaniasis (CL), which otherwise are difficult to achieve via oral and parenteral routes. Aim of this study was to develop rifampicin (RIF) and vancomycin (VAN) co-loaded transfersomes (RVCT) and further incorporate them into chitosan gel to allow the retention of RVCT to the infected skin and reduce the drugs toxicity. The RVCT was optimized for lipid to surfactant ratio, stirring speed and injection rate. Further, RVCT were assessed for their particle size (PS), zeta potential (ZP), polydispersity index (PDI) and entrapment efficiency. Moreover, the RVCT gel was optimized for its deformability index, in-vitro drug release and ex-vivo drug permeation. The in-vitro and in-vivo anti-leishmanial activities were also performed. The optimized formulation was nano-sized (167.9 ± 1.6), with better %EE of both RIF (58.51% ± 0.11) and VAN (86.18% ± 0.13). RVCT get demonstrated sustained release of the incorporated drugs. Ex-vivo permeation study showed better skin permeation of RVCT and RVCT gel without using permeation enhancers. The anti-leishmanial activity on in-vitro leishmania cultures of promastigotes and axenic amastigotes of L. tropica exhibited a 2.4 folds and 2.3 folds increased activity against promastigotes and axenic amastigotes, respectively. The in-vivo antileishmanial study demonstrated significantly reduced lesion size when treated with RVCT gel. These results clearly indicated the potential of RVCT gel in achieving targeted co-delivery of RIF and VAN for the treatment of CL, after topical application. © 2020 Elsevier B.V.