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

## TL;DR

This study explores a new drug delivery system using nanoassemblies to treat leishmaniasis, showing reduced toxicity and improved effectiveness in both lab and animal tests.

## Contribution

The novel use of chitosan-titanium dioxide-Glucantime nanoassemblies for treating leishmaniasis is introduced and tested.

## Key findings

- Nanoassemblies showed reduced cytotoxicity compared to Glucantime in macrophage cells.
- Treatment with nanoassemblies reduced lesion size and parasite burden in infected mice.
- Nanoassemblies modulated immune response by upregulating CCR7 and downregulating CD163.

## Abstract

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.

Cytotoxicity was evaluated in the J774.A1 macrophage cell line to determine the IC50 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).

The nanoassemblies treatment exhibited reduced cytotoxicity with a significantly higher IC50 (1202.5 ± 3.5 μg/ml at 72 hr) in comparison with Glucantime (999.5 ± 3.5 μg/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).

The findings highlight the potential of chitosan-titanium dioxide-Glucantime nanoassemblies as a promising therapeutic strategy against leishmaniasis.