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Low cytotoxicity of solid lipid nanoparticles in in vitro and ex vivo lung models

: Nassimi, M.; Schleh, C.; Lauenstein, H.-D.; Hussein, R.; Lübbers, K.; Pohlmann, G.; Switalla, S.; Sewald, K.; Müller, M.; Krug, N.; Müller-Goymann, C.C.; Braun, A.


Inhalation Toxicology 21 (2009), No.S1, pp.104-109
ISSN: 0895-8378
ISSN: 1091-7691
Journal Article
Fraunhofer ITEM ()
solid lipid nanoparticle; drug delivery; precision cut lung slice; lung toxicity

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 mug/ml and for SLN50 of 1520 mug/ml. The cytotoxicity in terms of LDH release showed comparable EC(50) values of 3431 mug/ml and 1253 mug/ml for SLN20 and SLN50, respectively. However, in PCLS we determined only SLN50 cytotoxic values with a concentration of 1500 mug/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.