Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM, Hannover, Germany.
Inhal Toxicol. 2009 Jul;21 Suppl 1:104-9. doi: 10.1080/08958370903005769.
The aim of this study was to investigate the potential cytotoxicity of solid lipid nanoparticles (SLN) for human lung as a suitable drug delivery system (DDS). Therefore we used a human alveolar epithelial cell line (A549) and murine precision-cut lung slices (PCLS) to estimate the tolerable doses of these particles for lung cells. A549 cells (in vitro) and precision-cut lung slices (ex vivo) were incubated with SLN20 (20% phospholipids in the lipid matrix of the particles) and SLN50 (50% phospholipids in the lipid matrix of the particles) in increasing concentrations. The cytotoxic effects of SLN were evaluated in vitro by lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Vitality of lung slices was controlled by staining with calcein AM/ethidium homodimer 1 using confocal laser scanning microscopy and followed by quantitative image analysis with IMARIS software. A549 cell line revealed a middle effective concentration (EC(50)) for MTT assay for SLN20 of 4080 microg/ml and for SLN50 of 1520 microg/ml. The cytotoxicity in terms of LDH release showed comparable EC(50) values of 3431 microg/ml and 1253 microg/ml for SLN20 and SLN50, respectively. However, in PCLS we determined only SLN50 cytotoxic values with a concentration of 1500 microg/ml. The lung slices seem to be a more sensitive test system. SLN20 showed lower toxic values in all test systems. Therefore we conclude that SLN20 could be used as a suitable DDS for the lung, from a toxicological point of view.
本研究旨在探讨固体脂质纳米粒（SLN）作为一种合适的药物传递系统（DDS）对人肺的潜在细胞毒性。因此，我们使用人肺泡上皮细胞系（A549）和鼠肺精密切割切片（PCLS）来估计这些颗粒对肺细胞的可耐受剂量。A549 细胞（体外）和精密切割肺切片（离体）用浓度递增的 SLN20（脂质基质中 20%的磷脂）和 SLN50（脂质基质中 50%的磷脂）孵育。通过乳酸脱氢酶（LDH）和 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴化物（MTT）测定法评估 SLN 的细胞毒性。使用钙黄绿素 AM/乙锭同源二聚体 1 对肺切片进行染色，通过共聚焦激光扫描显微镜进行活力控制，并使用 IMARIS 软件进行定量图像分析。A549 细胞系显示 MTT 测定法对 SLN20 的中效浓度（EC50）为 4080μg/ml，对 SLN50 的 EC50 为 1520μg/ml。LDH 释放的细胞毒性显示出 SLN20 和 SLN50 的 EC50 值分别为 3431μg/ml 和 1253μg/ml，具有可比性。然而，在 PCLS 中，我们仅确定了浓度为 1500μg/ml 的 SLN50 细胞毒性值。肺切片似乎是一种更敏感的测试系统。在所有测试系统中，SLN20 均显示出较低的毒性值。因此，从毒理学角度来看，我们得出结论，SLN20 可以作为肺部合适的 DDS 使用。
