Université Paris-Sud, Faculté de pharmacie, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue JB Clément, 92296 Chatenay-Malabry Cedex, France.
Int J Pharm. 2013 Oct 1;454(2):686-94. doi: 10.1016/j.ijpharm.2013.05.025. Epub 2013 Jun 6.
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(®) 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-α 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.
已经在 A549 人肺上皮细胞上研究了暴露于由聚（丙交酯-共-乙交酯）（PLGA）制成的纳米颗粒（NPs）后的体外细胞毒性和炎症反应。使用不同的稳定剂（聚乙烯醇、壳聚糖或 Pluronic®F68）获得了三种不同的 PLGA NPs（230nm），分别形成中性、正电荷或负电荷 NPs。聚苯乙烯 NPs 被用作聚合物但不可生物降解的 NPs，以及二氧化钛（锐钛矿和金红石）作为无机 NPs，用于比较。通过线粒体活性以及膜完整性（乳酸脱氢酶释放、台盼蓝排除、碘化丙啶染色）评估细胞毒性。PLGA 基和聚苯乙烯 NPs 的细胞毒性低于或与暴露于二氧化钛 NPs 后观察到的细胞毒性相当。通过释放白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）细胞因子评估的炎症反应对于所有 NPs 均较低。然而，观察到一些差异，尤其是对于带负电荷的 PLGA NPs，导致更高的炎症反应，这可以与这些 NPs 的更高摄取相关。总之，这些结果表明，PLGA NPs 的涂层和核的性质都在细胞反应中起着关键作用。
