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

  • Nassimi, Matthias
  • Schleh, Carsten
  • Lauenstein, Hans-Dieter
  • Hussein, Riem
  • Lübbers, Katrin
  • Pohlmann, Gerhard
  • Switalla, Simone
  • Sewald, Katherina
  • Müller, Meike
  • Krug, Norbert
  • Müller-Goymann, Christel C
  • Braun, Armin
Published Article
Inhalation toxicology
Publication Date
Jul 01, 2009
21 Suppl 1
DOI: 10.1080/08958370903005769
PMID: 19558241


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.

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