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

Abstract

Objective(s): Leishmaniasis, a neglected tropical disease, remains a public health concern. Meglumine antimonate (Glucantime (R)) 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 J774.A1 macrophage cell line to determine the IC(50 )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 M1 and M2 macrophage polarization markers (CCR7 and CD163). Results: The nanoassemblies treatment exhibited reduced cytotoxicity with a significantly higher IC50 (1202.5 +/- 3.5 Ng/ml at 72 hr) in comparison with Glucantime (999.5 +/- 3.5 Ng/mL at 72 hr; P<0.05). Treatment with nanoassemblies (100 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<0.05). 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 CCR7 expression (P<0.0001) and downregulation of CD163 expression (P<0.05). Conclusion: The findings highlight the potential of chitosan-titanium dioxide-Glucantime nanoassemblies as a promising therapeutic strategy against leishmaniasis.