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载多聚谷氨酸包覆银纳米粒子和抗坏血酸的多功能 PLGA 颗粒,具有抗氧化和长效抗菌活性。

Multifunctional PLGA particles containing poly(l-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity.

机构信息

Centre for Fine Particles Processing and Nanotechnologies, Institute of Technical Sciences of the Serbian Academy of Sciences and Arts, Knez Mihailova 35/IV, 11000 Belgrade, Serbia.

出版信息

Acta Biomater. 2014 Jan;10(1):151-62. doi: 10.1016/j.actbio.2013.08.030. Epub 2013 Aug 26.

DOI:10.1016/j.actbio.2013.08.030
PMID:23988864
Abstract

A water-soluble antioxidant (ascorbic acid, vitamin C) was encapsulated together with poly(l-glutamic acid)-capped silver nanoparticles (AgNpPGA) within a poly(lactide-co-glycolide) (PLGA) polymeric matrix and their synergistic effects were studied. The PLGA/AgNpPGA/ascorbic acid particles synthesized by a physicochemical method with solvent/non-solvent systems are spherical, have a mean diameter of 775 nm and a narrow size distribution with a polydispersity index of 0.158. The encapsulation efficiency of AgNpPGA/ascorbic acid within PLGA was determined to be >90%. The entire amount of encapsulated ascorbic acid was released in 68 days, and the entire amount of AgNpPGAs was released in 87 days of degradation. The influence of PLGA/AgNpPGA/ascorbic acid on cell viability, generation of reactive oxygen species (ROS) in HepG2 cells, as well as antimicrobial activity against seven different pathogens was investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated good biocompatibility of these PLGA/AgNpPGA/ascorbic acid particles. We measured the kinetics of ROS formation in HepG2 cells by a DCFH-DA assay, and found that PLGA/AgNpPGA/ascorbic acid caused a significant decrease in DCF fluorescence intensity, which was 2-fold lower than that in control cells after a 5h exposure. This indicates that the PLGA/AgNpPGA/ascorbic acid microspheres either act as scavengers of intracellular ROS and/or reduce their formation. Also, the results of antimicrobial activity of PLGA/AgNpPGA/ascorbic acid obtained by the broth microdilution method showed superior and extended activity of these particles. The samples were characterized using Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, zeta potential and particle size analysis. This paper presents a new approach to the treatment of infection that at the same time offers a very pronounced antioxidant effect.

摘要

一种水溶性抗氧化剂(抗坏血酸,维生素 C)被包裹在聚(L-谷氨酸)-封端的银纳米粒子(AgNpPGA)内,然后封装在聚(乳酸-共-乙醇酸)(PLGA)聚合物基质中,并研究了它们的协同作用。通过溶剂/非溶剂系统的物理化学方法合成的 PLGA/AgNpPGA/抗坏血酸颗粒是球形的,平均直径为 775nm,粒径分布较窄,多分散指数为 0.158。AgNpPGA/抗坏血酸在 PLGA 中的包封效率被确定为>90%。在 68 天内释放了全部包裹的抗坏血酸,而在 87 天的降解过程中释放了全部的 AgNpPGAs。研究了 PLGA/AgNpPGA/抗坏血酸对 HepG2 细胞活力、活性氧(ROS)生成以及对七种不同病原体的抗菌活性的影响。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)测定法表明这些 PLGA/AgNpPGA/抗坏血酸颗粒具有良好的生物相容性。我们通过 DCFH-DA 测定法测量了 HepG2 细胞中 ROS 形成的动力学,发现 PLGA/AgNpPGA/抗坏血酸导致 DCF 荧光强度显著降低,与对照组细胞相比,在 5 小时暴露后降低了 2 倍。这表明 PLGA/AgNpPGA/抗坏血酸微球要么作为细胞内 ROS 的清除剂,要么减少其形成。此外,通过肉汤微量稀释法获得的 PLGA/AgNpPGA/抗坏血酸的抗菌活性结果表明,这些颗粒具有优越且延长的活性。使用傅里叶变换红外光谱、场发射扫描电子显微镜、透射电子显微镜、Zeta 电位和粒径分析对样品进行了表征。本文提出了一种治疗感染的新方法,同时具有非常明显的抗氧化作用。

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