Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis

Topical delivery is preferable over systemic delivery for cutaneous leishmaniasis (CL), because of its easy administration, reduced systemic adverse effects, and low cost. Nitazoxanide (NTZ) has broad-spectrum activity against various parasites and has the potential to avoid drug resistance developed by enzymatic mutations. NTZ oral formulation is being associated with severe dyspepsia and stomach pain. Herein, NTZ-transethosomes (NTZ-TES) were prepared and loaded into chitosan gel (NTZ-TEG) for topical delivery. NTZ-TES were prepared by thin-film-hydration method and optimized statistically via Box-Behnken method. The optimized formulation indicated excellent particle size (176 nm), PDI (0.093), zeta potential (-26.4 mV) and entrapment efficiency (EE, 86%). The TEM analysis showed spherical sized particles and FTIR analysis indicated no interaction among the excipients. Similarly, NTZ-TEG showed optimal pH, desirable viscosity and good spreadability. NTZ-TES and NTZ-TEG showed prolonge...