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载药聚合物纳米囊的评估:不同包衣对雌性大鼠毒理学和行为学参数的影响。

Assessment of unloaded polymeric nanocapsules with different coatings in female rats: Influence on toxicological and behavioral parameters.

机构信息

Postgraduate Program in Pharmaceutical Sciences, Federal University of Pampa, Campus Uruguaiana, BR 472, Km 7, 97500-970, Uruguaiana, RS, Brazil.

Postgraduate Program in Biochemistry, Federal University of Pampa, UNIPAMPA, Uruguaiana, Brazil.

出版信息

Biomed Pharmacother. 2020 Jan;121:109575. doi: 10.1016/j.biopha.2019.109575. Epub 2019 Nov 2.

Abstract

The unloaded polymeric nanocapsules (NCs) present incredible characteristics as drug carriers. However, the toxicity caused by NCs with different coatings is still a challenge for contemporary toxicology. Allied to this, preclinical studies are performed in males, disregarding possible gender-dependent toxicity. Thus, the aim of present study was to evaluate the influence of different NCs coatings on toxicological and behavioral parameters in female rats. The physicochemical characterization of NCs with different surface coatings: NC1 (Polysorbate 80), NC2 (PEG), NC3 (Eudragit®RS 100) and NC4 (Chitosan) were performed. Female rats were treated with saline, NC1, NC2, NC3 or NC4 daily for 14 days, p.o. After 24 h of last treatment, animals were submitted to behavioral tests. Only after behavioral tests, female rats were euthanized, organs were removed and weighted. After, histopathological, biochemical and oxidative stress analysis were performed. All NCs-coatings did not cause alterations in behavioral tests. For markers of hepatic, renal damage and lipid profile, the different coatings showed a low toxicity. NCs did not alter weight of organs and histopathological analysis. Also, all NCs-coatings did not modify redox balance in organs studied, only NC2 induced a increase of FRAP levels in intestine. This study demonstrated that the different NCs-coatings did not cause behavioral changes and showed a low toxicity in female rats.

摘要

未载药的聚合物纳米囊(NCs)作为药物载体具有令人难以置信的特性。然而,不同涂层的 NCs 的毒性仍然是当代毒理学的一个挑战。此外,临床前研究通常在雄性动物中进行,而忽略了可能存在的性别依赖性毒性。因此,本研究旨在评估不同 NCs 涂层对雌性大鼠毒理学和行为参数的影响。对具有不同表面涂层的 NCs(NC1:聚山梨酯 80、NC2:PEG、NC3:Eudragit®RS 100 和 NC4:壳聚糖)进行了理化特性表征。雌性大鼠每天口服生理盐水、NC1、NC2、NC3 或 NC4 连续 14 天。最后一次处理 24 小时后,动物进行行为测试。只有在行为测试后,雌性大鼠才被安乐死,取出器官称重。然后进行组织病理学、生化和氧化应激分析。所有 NCs 涂层均未在行为测试中引起改变。对于肝、肾损伤和脂质谱标志物,不同的涂层显示出低毒性。NCs 不改变器官重量和组织病理学分析。此外,所有 NCs 涂层均未改变研究器官的氧化还原平衡,只有 NC2 诱导肠中 FRAP 水平升高。本研究表明,不同的 NCs 涂层不会引起行为改变,并在雌性大鼠中表现出低毒性。

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