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对白蛋白选择性纳米颗粒上预先形成的白蛋白冠层及其性能的洞察。

Insight into the preformed albumin corona on and performances of albumin-selective nanoparticles.

作者信息

Li Zhenbao, Li Dan, Zhang Wenjuan, Zhang Peng, Kan Qiming, Sun Jin

机构信息

Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.

The College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.

出版信息

Asian J Pharm Sci. 2019 Jan;14(1):52-62. doi: 10.1016/j.ajps.2018.07.002. Epub 2018 Aug 9.

Abstract

Preformed albumin corona of albumin-nonselective nanoparticles (NPs) is widely exploited to inhibit the unavoidable protein adsorption upon intravenous administration. However, very few studies have concerned the preformed albumin corona of albumin-selective NPs. Herein, we report a novel type of albumin-selective NPs by decorating 6-maleimidocaproyl polyethylene glycol stearate (SA) onto PLGA NPs (SP NPs) surface, taking albumin-nonselective PLGA NPs as control. PLGA NPs and SP NPs were prepared by emulsion-solvent evaporation method and the resultant NPs were in spherical shape with an average diameter around 180 nm. The corresponding albumin-coating PLGA NPs (PLGA@BSA NPs) and albumin-coating SP NPs (SP@BSA NPs) were formulated by incubating SP NPs or PLGA NPs with bovine serum albumin solution, respectively. The impact of albumin corona on particle characteristics, stability, photothermal effect, cytotoxicity, cell uptake, spheroid penetration and pharmacokinetics was investigated. In line with previous findings of preformed albumin coating, PLGA@BSA NPs exhibited higher stability, cytotoxicity, cell internalization and spheroid penetration performances , and longer blood circulation time than those of albumin-nonselective PLGA NPs, but albumin-selective SP NPs is capable of achieving a comparable and performances with both SP@BSA NPs and PLGA@BSA NPs. Our results demonstrate that SA decorated albumin-selective NPs pave a versatile avenue for optimizing nanoparticulate delivery without preformed albumin corona.

摘要

白蛋白非选择性纳米颗粒(NPs)的预形成白蛋白冠层被广泛用于抑制静脉给药时不可避免的蛋白质吸附。然而,很少有研究关注白蛋白选择性NPs的预形成白蛋白冠层。在此,我们报道了一种新型的白蛋白选择性NPs,通过将6-马来酰亚胺己酰聚乙二醇硬脂酸酯(SA)修饰到聚乳酸-羟基乙酸共聚物(PLGA) NPs(SP NPs)表面,以白蛋白非选择性的PLGA NPs作为对照。采用乳液-溶剂蒸发法制备PLGA NPs和SP NPs,所得NPs呈球形,平均直径约为180nm。通过分别将SP NPs或PLGA NPs与牛血清白蛋白溶液孵育,制备相应的白蛋白包被PLGA NPs(PLGA@BSA NPs)和白蛋白包被SP NPs(SP@BSA NPs)。研究了白蛋白冠层对颗粒特性、稳定性、光热效应、细胞毒性、细胞摄取、球体穿透和药代动力学的影响。与先前关于预形成白蛋白包被的研究结果一致,PLGA@BSA NPs表现出比白蛋白非选择性PLGA NPs更高的稳定性、细胞毒性、细胞内化和球体穿透性能,以及更长的血液循环时间,但白蛋白选择性SP NPs能够与SP@BSA NPs和PLGA@BSA NPs实现相当的性能。我们的结果表明,SA修饰的白蛋白选择性NPs为优化无预形成白蛋白冠层的纳米颗粒递送开辟了一条通用途径。

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