Designing, Optimization and Characterization of Trifluralin Transfersomal Gel to Passively Target Cutaneous Leishmaniasis.

Herein, Trifluralin (TFL) laden transfersomes (TFS) were investigated against Cutaneous Leishmaniasis (CL), via localized and targeted dermal delivery of TFL. Designed TFL-TFS were optimized utilizing 23 full factorial design on the basis of desired response factors including Particle size (P.S), Polydispersity index (PDI), TFL entrapment (%EE) and deformability index (DI). Optimized formulation was found to display P.S of 140.3 ± 2.3, PDI of 0.006 ± 0.002, %EE of 86 ± 0.5 and 43.5 ± 1.0 DI. Results of TEM and XRD analysis have shown intact spherical structure of TFL-TFS and alteration in TFL crystallinity, respectively. Moreover, the optimized TFL-TFS were loaded in Carbopol-940 gel to attain protracted skin retention. TFL-TFS were found to exhibit sustain TFL release profile for up to 24 h. Ameliorated skin permeation of TFL-TFS, even in absence of permeation enhancers, has shown its suitability for cutaneous application. Macrophage uptake assay demonstrated higher intracellular penetration, evidenced by intense reddish fluorescence of rhodamine loaded TFS in comparison to rhodamine-solution. In vitro anti-leishmanial assessment was showing 2.86-folds and 3.07-folds decrement in IC50-value of TFL-TFS against L. tropica KWH23 amastigotes and promastigotes, respectively. Percent inhibition assay against intra-macrophage amastigotes demonstrated that 90.87% amastigotes were assassinated at 50 μg/ml concentration of TFL-TFS, in comparison to the plain TFL-solution, exhibiting 54% parasitic killing.