Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis

Abstract

Topical delivery is preferable over systemic delivery for cutaneous leishmaniasis, 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 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 the thin-film hydration method and optimized statistically via the Box-Behnken method. The optimized formulation indicated excellent particle size (176 nm), polydispersity index (0.093), zeta potential (−26.4 mV) and entrapment efficiency (86%). The transmission electron microscopy analysis showed spherical-sized particles and Fourier-transform infrared spectroscopy analysis indicated no interaction among the excipients. Similarly, NTZ-TEG showed optimal pH, desirable viscosity and good spreadability. NTZ-TES and NTZ-TEG showed prolonged release behaviour and higher skin penetration and deposition in the epidermal/dermal layer of skin in comparison with the NTZ-dispersion. Moreover, NTZ-TES showed higher percentage inhibition, lower half-maximal inhibitory concentration (IC 50 ) against promastigotes and higher macrophage uptake. Additionally, skin irritation and histopathology studies indicated the safe and non-irritant behaviour of the NTZ-TEG. The obtained findings suggested the enhanced skin permeation and improved anti-leishmanial effect of NTZ when administered as NTZ-TEG.

Nitazoxanide: A Drug Repositioning Compound with Potential Use in Chagas Disease in a Murine Model

“…The nitazoxanide-treated group presented a lower average body weight than all of the other groups, most likely due to some side effects of the drug (anorexia, diarrhea, and nausea) that probably caused a lower feed intake and weight loss, or a direct catabolic effect of the drug, since some studies showed that although it can be well tolerated due to its good safety profile, it may be associated of adverse reactions, especially when prolonged and increased oral doses are administered [ 26 , 27 , 28 ].…”

Investigation of the treatment potential of Raloxifene-loaded polymeric nanoparticles in osteoporosis: In-vitro and in-vivo analyses

“…Suitable dilutions of the samples were prepared and analyzed using HPLC as discussed above for the quantification of RLX and the release graphs were drawn using Sigma plot software. Additionally, DD-Solver was used to check the best fitted release model [ 37 , 38 ].…”

Exploring the potential of transethosomes in therapeutic delivery: A comprehensive review

“…Still, the zeta potential value is increased, indicating stability and a threefold increase in EE, which may be due to reduced polarity by combining deoxycholate anion and drug cation. 37 Salem et al 1 and Khalid et al 38 study revealed that increasing surfactant concentration could cause a substantial decrease in the vesicle size due to interfacial tension being reduced by high surfactant levels covering the carrier surface. This Tween 80 effect results in its solubilizing property and inhibition of vesicle cohesion.…”