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PLGA 纳米粒作为药物传递系统的体内分布和安全性评价。

In vivo evaluation of the biodistribution and safety of PLGA nanoparticles as drug delivery systems.

机构信息

Council of Scientific and Industrial Research, Polymers and Bioceramics, Pretoria, South Africa.

出版信息

Nanomedicine. 2010 Oct;6(5):662-71. doi: 10.1016/j.nano.2010.02.002. Epub 2010 Mar 15.

Abstract

UNLABELLED

The remarkable physicochemical properties of particles in the nanometer range have been proven to address many challenges in the field of science. However, the possible toxic effects of these particles have raised some concerns. The aim of this article is to evaluate the effects of poly(lactide-co-glycolide) (PLGA) nanoparticles in vitro and in vivo compared to industrial nanoparticles of a similar size range such as zinc oxide, ferrous oxide, and fumed silica. An in vitro cytotoxicity study was conducted to assess the cell viability following exposure to PLGA nanoparticles. Viability was determined by means of a WST assay, wherein cell viability of greater than 75% was observed for both PLGA and amorphous fumed silica particles and ferrous oxide, but was significantly reduced for zinc oxide particles. In vivo toxicity assays were performed via histopathological evaluation, and no specific anatomical pathological changes or tissue damage was observed in the tissues of Balb/C mice. The extent of tissue distribution and retention following oral administration of PLGA particles was analyzed for 7 days. After 7 days, the particles remained detectable in the brain, heart, kidney, liver, lungs, and spleen. The results show that a mean percentage (40.04%) of the particles were localized in the liver, 25.97% in the kidney, and 12.86% in the brain. The lowest percentage was observed in the spleen. Thus, based on these assays, it can be concluded that the toxic effects observed with various industrial nanoparticles will not be observed with particles made of synthetic polymers such as PLGA when applied in the field of nanomedicine. Furthermore, the biodistribution of the particles warrants surface modification of the particles to avoid higher particle localization in the liver.

FROM THE CLINICAL EDITOR

The aim of this study was to evaluate the effects of poly(lactide-co-glycolide) (PLGA) nanoparticles in vitro and in vivo compared to industrial nanoparticles including zinc oxide, ferrous oxide, and fumed silica. The authors concluded that the toxic effects observed with various industrial nanoparticles is unlikely to be observed with particles made of PLGA. The biodistribution of these particles warrants surface modification to avoid particle accumulation in the liver.

摘要

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纳米范围内颗粒的显著物理化学性质已被证明可以解决科学领域的许多挑战。然而,这些颗粒可能具有的毒性作用引起了一些关注。本文的目的是评估聚(乳酸-共-乙醇酸)(PLGA)纳米粒子与具有相似尺寸范围的工业纳米粒子(如氧化锌、氧化亚铁和气相法二氧化硅)相比在体外和体内的影响。进行了体外细胞毒性研究,以评估暴露于 PLGA 纳米粒子后细胞活力。通过 WST 测定法确定细胞活力,其中观察到 PLGA 和无定形气相法二氧化硅颗粒以及氧化亚铁的细胞活力大于 75%,但氧化锌颗粒的细胞活力显著降低。通过组织病理学评估进行了体内毒性试验,在 Balb/C 小鼠的组织中未观察到特定的解剖病理变化或组织损伤。分析了口服 PLGA 颗粒 7 天后的组织分布和保留程度。7 天后,仍可在大脑、心脏、肾脏、肝脏、肺脏和脾脏中检测到颗粒。结果表明,颗粒的平均百分比(40.04%)定位于肝脏,25.97%定位于肾脏,12.86%定位于大脑。脾脏中观察到的百分比最低。因此,根据这些试验,可以得出结论,当在纳米医学领域应用时,与各种工业纳米粒子观察到的毒性作用不会与由合成聚合物如 PLGA 制成的颗粒观察到的毒性作用。此外,颗粒的生物分布需要对颗粒进行表面改性,以避免颗粒在肝脏中的更高定位。

临床编辑按

本研究的目的是评估聚(乳酸-共-乙醇酸)(PLGA)纳米粒子与包括氧化锌、氧化亚铁和气相法二氧化硅在内的工业纳米粒子在体外和体内的影响。作者得出结论,与各种工业纳米粒子观察到的毒性作用相比,PLGA 制成的颗粒不太可能观察到毒性作用。这些颗粒的生物分布需要进行表面改性,以避免颗粒在肝脏中的积累。

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