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载有对,对'-甲氧基二苯基二硒化物的聚合物纳米胶囊化学性质稳定,且不会在小鼠体内诱发毒性。

p,p'-Methoxyl-diphenyl diselenide-loaded polymeric nanocapsules are chemically stable and do not induce toxicity in mice.

作者信息

Marcondes Sari Marcel Henrique, Ferreira Luana Mota, Zborowski Vanessa Angonesi, Araujo Paulo Cesar Oliveira, Cervi Verônica Ferrari, Brüning César Augusto, Cruz Letícia, Nogueira Cristina Wayne

机构信息

Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Programa de Pós-graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.

Programa de Pós-graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.

出版信息

Eur J Pharm Biopharm. 2017 Aug;117:39-48. doi: 10.1016/j.ejpb.2017.03.018. Epub 2017 Mar 28.

Abstract

Organoselenium compounds have been targeted to new therapeutic tools development due to their pharmacological actions. However, some toxicity issues and physicochemical limitations delay the clinical application of these compounds. The incorporation of organoselenium molecules into nanostructured systems arises as a promising alternative to overcome such restrictions. The current study proposed the characterization of the polymeric nanocapsules of p,p'-methoxyl-diphenyl diselenide [(OMePhSe)] as well as the evaluation of the in vivo toxicity and biodistribution profile. The nanocapsules, which were composed by medium-chain triglycerides as the oil core and poly(ε-caprolactone) as the polymeric wall, showed nanometric size (236±4), low polydispersity (<0.2), negative zeta potential (-5.4±0.06), neutral pH values (7.2±0.08) and a high encapsulation efficiency (98%). Besides, the nanoencapsulation process increased the (OMePhSe) stability. The repeated intragastric administration of (OMePhSe) nanoencapsulated (25mg/kg/day during 7days) did not cause any alteration in the oxidative status, hematological parameters, and plasma biochemical markers of cellular damage. Moreover, the (OMePhSe) incorporation into nanocapsules increased the selenium concentrations in the tissues (kidneys, liver and plasma) suggesting an improvement in its oral bioavailability.

摘要

由于其药理作用,有机硒化合物已成为新型治疗工具开发的目标。然而,一些毒性问题和物理化学限制阻碍了这些化合物的临床应用。将有机硒分子纳入纳米结构系统是克服此类限制的一种有前景的替代方法。当前的研究提出了对p,p'-甲氧基二苯基二硒化物[(OMePhSe)]的聚合物纳米胶囊进行表征,以及评估其体内毒性和生物分布情况。该纳米胶囊由中链甘油三酯作为油相核心和聚(ε-己内酯)作为聚合物壁组成,呈现出纳米尺寸(236±4)、低多分散性(<0.2)、负zeta电位(-5.4±0.06)、中性pH值(7.2±0.08)以及高包封率(98%)。此外,纳米包封过程提高了(OMePhSe)的稳定性。重复灌胃给予纳米包封的(OMePhSe)(25mg/kg/天,持续7天)并未引起氧化状态、血液学参数以及细胞损伤的血浆生化标志物的任何改变。此外,将(OMePhSe)纳入纳米胶囊提高了组织(肾脏、肝脏和血浆)中的硒浓度,表明其口服生物利用度有所提高。

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