Iranian journal of basic medical sciences · 2025
Effects of chitosan-titanium dioxide-Glucantime nanoassemblies on Leishmania major: An in vitro and in vivo study.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Tavakoli Sanaz, Varshosaz Jaleh, Saberi Sedigheh, Kazemi Mohammad, Nematollahi Pardis, Pestehchian Nader
Аннотация
OBJECTIVES: 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 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).
RESULTS: 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).
CONCLUSION: The findings highlight the potential of chitosan-titanium dioxide-Glucantime nanoassemblies as a promising therapeutic strategy against leishmaniasis.
MATERIALS AND METHODS: 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).
RESULTS: 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).
CONCLUSION: The findings highlight the potential of chitosan-titanium dioxide-Glucantime nanoassemblies as a promising therapeutic strategy against leishmaniasis.