Effects of chitosan-titanium dioxide-Glucantime nanoassemblies on Leishmania major: An in vitro and in vivo study

Objective(s): Leishmaniasis, a neglected tropical disease, remains a public health concern. Meglumine antimonate (Glucantime®) is associated with high toxicity, prolonged treatment duration, and the emergence of drug resistance. This study aims to investigate a therapeutic strategy using chitosan-titanium dioxide-Glucantime (C-TiO₂-G) nanoassemblies comprising the natural polymer chitosan for drug loading, TiO₂ nanoparticles for enhanced cellular uptake, and Glucantime as the antileishmanial agent. Materials and Methods: Cytotoxicity was evaluated in the J۷۷۴.A۱ macrophage cell line to determine the IC۵۰ values, and anti-leishmanial activity against Leishmania major (L. major) amastigotes was assessed using the Giemsa staining method. Lesion size, parasite burden, and tissue histopathology were monitored in BALB/c mice. Additionally, gene expression analysis was conducted to assess the expression of M۱ and M۲ macrophage polarization markers (CCR۷ and CD۱۶۳). Results: The nanoassemblies treatment exhibited reduced cytotoxicity with a significantly higher IC۵۰ (۱۲۰۲.۵ ± ۳.۵ μg/ml at ۷۲ hr) in comparison with Glucantime (۹۹۹.۵ ± ۳.۵ μg/mL at ۷۲ hr; P<۰.۰۵). Treatment with nanoassemblies (۱۰۰ mg/kg) significantly reduced lesion size and parasite burden in the spleen and liver of the L. major-infected BALB/c mice compared with those in the negative control group (P<۰.۰۵). Histopathological analysis revealed less tissue damage in the liver, skin, spleen, and lymph nodes. Treatment with nanoassemblies led to immune modulation, as indicated by significant upregulation of CCR۷ expression (P<۰.۰۰۰۱) and downregulation of CD۱۶۳ expression (P<۰.۰۵).Conclusion: The findings highlight the potential of chitosan-titanium dioxide-Glucantime nanoassemblies as a promising therapeutic strategy against leishmaniasis.

کلیدواژه ها:

Antileishmanial therapeutics ، Drug delivery systems ، Drug resistance in - leishmaniasis ، Leishmania major ، Leishmaniasis treatment - strategies ، Titanium dioxide - nanoparticles