Toxicity of surface-modified PLGA nanoparticles toward lung alveolar epithelial cells

Toxicity of surface-modified PLGA nanoparticles toward lung alveolar epithelial cells
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DOI:
10.1016/j.ijpharm.2013.05.025
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发表时间:
2013-10-01
影响因子:
5.8
通讯作者:
Fattal, Elias
Fattal, Elias
中科院分区:
医学2区
文献类型:
--
作者:
Grabowski, Nadege;Hillaireau, Herve;Fattal, Elias

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研究了聚丙交酯-乙交酯共聚物(PLGA)纳米微粒对人肺上皮细胞A549的体外细胞毒性和炎症反应。用不同的稳定剂(聚乙烯醇、壳聚糖或Pluronic(R)F68)制备了三种不同的PLGA纳米粒子(230 Nm),分别形成中性、带正电荷或带负电荷的NPs。将聚苯乙烯纳米粒子作为聚合物但不可生物降解的纳米粒子,二氧化钛(锐钛矿型和金红石型)作为无机纳米粒子进行比较。通过线粒体活性和膜完整性(乳酸脱氢酶释放、台盼蓝排斥、碘化丙啶染色)评价细胞毒性。PLGA和聚苯乙烯纳米颗粒的细胞毒性低于或相当于二氧化钛纳米颗粒暴露后的细胞毒性。通过释放IL-6、IL-8、MCP-1、TNF-α细胞因子来评估炎症反应,所有NPs的炎症反应都很低。然而,观察到了一些差异,特别是在PLGA阴性的NPs导致更高的炎症反应,这可能与这些NPs的更高摄取相关。综上所述,这些结果表明PLGA纳米颗粒的包被和核心的性质在细胞响应中起着关键作用。(C)2013爱思唯尔B.V.保留所有权利。
In vitro cytotoxicity and inflammatory response following exposure to nanoparticles (NPs) made of poly(lactide-co-glycolide) (PLGA) have been investigated on A549 human lung epithelial cells. Three different PLGA NPs (230 nm) were obtained using different stabilizers (polyvinyl alcohol, chitosan, or Pluronic (R) F68) to form respectively neutral, positively or negatively charged NPs. Polystyrene NPs were used as polymeric but non-biodegradable NPs, and titanium dioxide (anatase and rutile) as inorganic NPs, for comparison. Cytotoxicity was evaluated through mitochondrial activity as well as membrane integrity (lactate dehydrogenase release, trypan blue exclusion, propidium iodide staining). The cytotoxicity of PLGA-based and polystyrene NPs was lower or equivalent to the one observed after exposure to titanium dioxide NPs. The inflammatory response, evaluated through the release of the IL-6, IL-8, MCP-1, TNF-alpha cytokines, was low for all NPs. However, some differences were observed, especially for negative PLGA NPs that led to a higher inflammatory response, which can be correlated to a higher uptake of these NPs. Taken together, these results show that both coating of PLGA NPs and the nature of the core play a key role in cell response. (C) 2013 Elsevier B. V. All rights reserved.