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固体脂质纳米粒的体外生物相容性。

In vitro biocompatibility of solid lipid nanoparticles.

机构信息

Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina P.O. Box 476, Florianópolis, SC, 88040-900, Brazil.

出版信息

Sci Total Environ. 2012 Aug 15;432:382-8. doi: 10.1016/j.scitotenv.2012.06.018. Epub 2012 Jul 1.

DOI:10.1016/j.scitotenv.2012.06.018
PMID:22750185
Abstract

This study was undertaken to address the current deficient knowledge of cellular response to solid lipid nanoparticles (SLNs) exposure. We investigated the cytotoxicity of several SLNs formulations in two fibroblast cell lineages, Vero and MDCK. Several methods were used to explore the mechanisms involved in this cytotoxic process, including cell viability assays, flow cytometry and ROS generation assessment. Among nanoparticles tested, two of them (F4 and F5) demonstrated more cytotoxic effects in both cell lineages. The cell viability assays suggested that F4 and F5 interfere in cell mitochondrial metabolism and in lysosomal activity. In addition, F5 decreased the percentage of MDCK cells in G0/G1 and G2/M phases, with a marked increase in the Sub/G1 population, suggesting DNA fragmentation. Regarding F4, although IC(50) was higher (~700 μg/mL), this formulation affected mitochondrial membrane potential for Vero cells. However, the IC(50) of F5 was around 250 μg/mL, suggesting the effect of SDS (sodium dodecyl sulfate) present in the formulation. In summary, the nanoparticles tested here appears to be biocompatible, with the exception of F5. Further studies are required to elucidate the in vivo effects of these nanoscale structures, in order to evaluate or predict the connotation of their increased and widespread use.

摘要

本研究旨在解决目前对固体脂质纳米粒(SLN)暴露后细胞反应的知识不足的问题。我们研究了两种成纤维细胞系(Vero 和 MDCK)中几种 SLN 配方的细胞毒性。我们使用了多种方法来探讨这种细胞毒性过程中涉及的机制,包括细胞活力测定、流式细胞术和 ROS 生成评估。在测试的纳米粒子中,有两种(F4 和 F5)在两种细胞系中表现出更强的细胞毒性。细胞活力测定表明,F4 和 F5 干扰了细胞线粒体代谢和溶酶体活性。此外,F5 降低了 MDCK 细胞在 G0/G1 和 G2/M 期的比例,Sub/G1 群体明显增加,提示 DNA 片段化。对于 F4,尽管 IC(50)较高(~700 μg/mL),但该配方影响了 Vero 细胞的线粒体膜电位。然而,F5 的 IC(50)约为 250 μg/mL,表明配方中存在 SDS(十二烷基硫酸钠)的影响。总之,除 F5 外,这里测试的纳米粒子似乎是生物相容的。需要进一步研究以阐明这些纳米结构的体内效应,以便评估或预测其广泛使用所带来的影响。

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