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基于瑞舒伐他汀的壳聚糖纳米粒治疗急性弓形虫病的疗效评价:一项体外与体内研究。

Evaluation of the efficacy of Chitosan nanoparticles based on Rosuvastatin in the treatment of acute toxoplasmosis: An In vitro and In vivo study.

机构信息

Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Microb Pathog. 2024 Oct;195:106897. doi: 10.1016/j.micpath.2024.106897. Epub 2024 Aug 28.

DOI:10.1016/j.micpath.2024.106897
PMID:39208959
Abstract

Toxoplasma gondii (T.gondii) is an obligate intracellular protozoan that infects warm-blooded animals and has a global distribution. Acute toxoplasmosis is commonly reported in patients with acquired/congenital toxoplasmosis and immune deficiency. New methods are needed to prevent the sideffects of classical treatment. In this study, Rosuvastatin loaded chitosan nanoparticle (CH-NP-ROS) were synthesized and zeta potential and size were determined, and an MTT assay was performed to evaluate the cell toxicity on Macrophage cells (MQ) and anti-Toxoplasma activity using Trypan-blue staining by different concentrations of Rosuvastatin (ROS), and Rosuvastatin loaded chitosan nanoparticle (CH-NP-ROS). The cell viability assay demonstrated that CH-NP-ROS had lower cell toxicity (<15 %) compared to ROS (<30 %). Statistical analysis showed that CH-NP-ROS significantly killed 98.950 ± 1.344; P < 0.05) of Toxoplasma gondii tachyzoites. In vivo results of perituneal fluid showed that CH-NP significantly reduced the parasite load in the CH-NP-ROS group, compared to that in negative control group (P < 0.001). Growth inhibition rates of tachyzoites in mice receiving free ROS and CH-NP-ROS (injection and oral form) were found to be 166.125 + 4.066, 118.750 + 4.596 and 124.875 + 2.652, respectively, compared to mice in Sulfadiazine/Pyrimethamine treated group (positive control). In the infected untreated mice (control +), the mean tachyzoite counts per oil immersion field in the spleen was 8.25 respectively. The mean survival time in all the groups treated with ROS and CH-NP-ROS was longer than that in the negative control group Therefore, nanoformulation is a promising approach for the delivery and is safe for using therapeutic effects in acute toxoplasmosis.

摘要

刚地弓形虫(T.gondii)是一种专性细胞内原生动物,感染温血动物,分布广泛。获得性/先天性弓形虫病和免疫缺陷患者常报告急性弓形虫病。需要新的方法来预防经典治疗的副作用。在这项研究中,合成了载罗舒伐他汀壳聚糖纳米粒(CH-NP-ROS),并测定了其zeta 电位和粒径,通过不同浓度的罗舒伐他汀(ROS)和载罗舒伐他汀壳聚糖纳米粒(CH-NP-ROS)进行噻唑蓝染色,用 MTT 法评估对巨噬细胞(MQ)的细胞毒性和抗弓形虫活性。细胞活力测定表明,CH-NP-ROS 的细胞毒性低于 ROS(<15%)。统计学分析显示,CH-NP-ROS 可显著杀死 98.950±1.344 的弓形虫速殖子(P<0.05)。腹腔液的体内结果表明,与阴性对照组相比,CH-NP 显著降低了 CH-NP-ROS 组的寄生虫载量(P<0.001)。接受游离 ROS 和 CH-NP-ROS(注射和口服)的小鼠速殖子生长抑制率分别为 166.125+4.066、118.750+4.596 和 124.875+2.652,而磺胺嘧啶/乙胺嘧啶治疗组(阳性对照组)的生长抑制率为 124.875+2.652。在未感染未经治疗的小鼠(对照+)中,每个油浸场的速殖子数分别为 8.25。所有用 ROS 和 CH-NP-ROS 治疗的组的平均存活时间均长于阴性对照组。因此,纳米制剂是一种有前途的传递方法,用于治疗急性弓形虫病是安全的。

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