Mazzarino Letícia, Loch-Neckel Gecioni, Dos Santos Bubniak Lorena, Ourique Fabiana, Otsuka Issei, Halila Sami, Curi Pedrosa Rozangela, Santos-Silva Maria Cláudia, Lemos-Senna Elenara, Curti Muniz Edvani, Borsali Redouane
*Departamento de Ciências Farmacêuticas,
*Departamento de Ciências Farmacêuticas.
Toxicol Sci. 2015 Sep;147(1):104-15. doi: 10.1093/toxsci/kfv114. Epub 2015 Jun 5.
Xyloglucan-block-polycaprolactone (XGO-PCL) copolymer nanoparticles have been proposed as nanocarriers for drug delivery. However, the possible harmful effects of exposure to nanoparticles still remain a concern. Therefore, the aim of this study is to evaluate the potential toxicity of XGO-PCL nanoparticles using in vitro and in vivo assays. Cytotoxicity and genotoxicity studies were conducted on MRC-5 human fetal lung fibroblast cells upon exposure to XGO-PCL nanoparticles. No significant reduction in the cell viability and no DNA damage were observed at the different concentrations tested. Erythrocyte toxicity was assessed by the incubation of nanoparticles with human blood. XGO-PCL nanoparticles induced a hemolytic ratio of less than 1%, indicating good blood compatibility. Finally, the subacute toxicity of XGO-PCL nanoparticles (10 mg/kg/day) was evaluated in BALB/c mice when administered orally or intraperitoneally for 14 days. Results of the in vivo toxicity study showed no clinical signs of toxicity, mortality, weight loss, or hematological and biochemical alterations after treatment with nanoparticles. Also, microscopic analysis of the major organs revealed no histopathological abnormalities, corroborating the previous results. Thus, it can be concluded that XGO-PCL nanoparticles induced no effect indicative of toxicity, indicating their potential use as drug delivery systems.
木葡聚糖嵌段聚己内酯(XGO-PCL)共聚物纳米颗粒已被提议作为药物递送的纳米载体。然而,接触纳米颗粒可能产生的有害影响仍然令人担忧。因此,本研究的目的是使用体外和体内试验来评估XGO-PCL纳米颗粒的潜在毒性。对暴露于XGO-PCL纳米颗粒的MRC-5人胎儿肺成纤维细胞进行了细胞毒性和遗传毒性研究。在测试的不同浓度下,未观察到细胞活力的显著降低和DNA损伤。通过纳米颗粒与人血孵育来评估红细胞毒性。XGO-PCL纳米颗粒诱导的溶血率小于1%,表明具有良好的血液相容性。最后,当以10毫克/千克/天的剂量口服或腹腔注射给药14天时,评估了XGO-PCL纳米颗粒对BALB/c小鼠的亚急性毒性。体内毒性研究结果显示,用纳米颗粒治疗后,没有毒性的临床迹象、死亡率、体重减轻或血液学和生化改变。此外,对主要器官的显微镜分析未发现组织病理学异常,证实了先前的结果。因此,可以得出结论,XGO-PCL纳米颗粒未诱导出表明毒性的效应,表明它们作为药物递送系统具有潜在用途。