Nanoemulgel mediated enhanced skin curcumin penetration/retention for local treatment of cutaneous leishmaniasis: in vitro and in vivo assessment

Background Skin delivery of a therapeutically effective drug is imperative for local cutaneous leishmaniasis (CL) treatment.Objective This study aimed to formulate, optimize, and characterize curcumin-loaded nanoemulgel for enhanced skin drug retention to treat CL locally.Methods Nanoemulsions were prepared by high-speed homogenization, characterized, and optimized for size, PDI, zeta potential, stability, morphology, drug contents, encapsulation efficiency, in vitro drug release, antileishmanial activity, and cell viability. The optimized nanoemulsion (C3) was then incorporated into a carbopol-based gel and evaluated for pH, viscosity, spreadability, and in vitro drug release. Both formulations were then assessed for ex-vivo and in vivo skin permeation/retention, and pharmacokinetic analysis.Results All nanoemulsion formulations had size in nano range with negative surface charge, homogeneously distributed, with spherical droplet geometries, where C3 being highly stable, had good encapsulation efficiency and drug contents (85 ± 5.4 and 68 ± 3.2%), released 90% of drug within 4 h, while C3 gel released the drug significantly sustained up to 46% in 24 h. The C3 formulation demonstrated significant in vitro antileishmanial activity across all tested concentrations, while the IC50 value against NIH3T3 fibroblasts was 0.6202 mM (Log IC50: 2.7, R2: 0.98). The C3 gel showed significantly low skin permeation (341.7 ± 43.6 and 52.6 ± 8.9 µg) with significantly higher skin drug retention (129.5 ± 16.7 and 190.2 ± 33.4 µg) ex-vivo and in vivo, with significantly lower Cmax, AUC0-t, and AUC0-∞.Conclusion These results suggested that curcumin nanoemulgel could be an effective alternative strategy for treating CL locally.