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调控氧化锌纳米颗粒的药代动力学及其在体内的命运。

Modulation of the pharmacokinetics of zinc oxide nanoparticles and their fates in vivo.

机构信息

Department of Food Science and Technology, Seoul Women's University, 621 Hwarang-ro, Nowon-gu, Seoul 139-774, Republic of Korea.

出版信息

Nanoscale. 2013 Dec 7;5(23):11416-27. doi: 10.1039/c3nr02140h.

Abstract

In the present study, the effects of particle size (20 nm or 70 nm) and surface charge (negative or positive) on the pharmacokinetics, tissue distributions, and excretion of ZnO nanoparticles were examined following the administration of a single oral dose to rats. Pharmacokinetic profiles and biodistributions were not affected by particle size or gender. However, ZnO (-) particles were markedly more absorbed by the systemic circulation than ZnO (+) particles. Furthermore, the kinetic behaviors of ZnO nanoparticles differed from those of zinc ions, as evidenced by the low dissolution (13-14%) of ZnO nanoparticles under gastric conditions. The kidneys, liver, and lungs were found to be target organs. However, the major biological fate of ZnO nanoparticles in tissues was the ionic form, not the particulate form, and this was independent of exposure routes (oral and intravenous). Particle size was only found to affect excretion kinetics, and 20 nm particles were more rapidly eliminated. Most nanoparticles were excreted via the biliary and fecal routes, but a small amount of the nanoparticles was excreted via urine. The study shows that surface charge, rather than particle size or gender, is the critical modulator of the pharmacokinetic behavior of ZnO nanoparticles.

摘要

在本研究中,通过给大鼠单次口服给药,研究了粒径(20nm 或 70nm)和表面电荷(负或正)对 ZnO 纳米粒子的药代动力学、组织分布和排泄的影响。粒径和性别对药代动力学特征和生物分布没有影响。然而,与 ZnO(+)颗粒相比,ZnO(-)颗粒明显更容易被全身循环吸收。此外,ZnO 纳米颗粒的动力学行为与锌离子不同,这表明 ZnO 纳米颗粒在胃条件下的溶解率较低(13-14%)。研究发现肾脏、肝脏和肺部是靶器官。然而,组织中 ZnO 纳米颗粒的主要生物学命运是离子形式,而不是颗粒形式,这与暴露途径(口服和静脉内)无关。研究发现,只有粒径会影响排泄动力学,20nm 的颗粒排泄更快。大多数纳米颗粒通过胆汁和粪便途径排泄,但少量纳米颗粒通过尿液排泄。该研究表明,表面电荷而不是粒径或性别是调节 ZnO 纳米颗粒药代动力学行为的关键因素。

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