PMID- 19558241 OWN - NLM STAT- MEDLINE DCOM- 20100201 LR - 20090629 IS - 1091-7691 (Electronic) IS - 0895-8378 (Linking) VI - 21 Suppl 1 DP - 2009 Jul TI - Low cytotoxicity of solid lipid nanoparticles in in vitro and ex vivo lung models. PG - 104-9 LID - 10.1080/08958370903005769 [doi] AB - 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. FAU - Nassimi, Matthias AU - Nassimi M AD - Fraunhofer-Institut fur Toxikologie und Experimentelle Medizin ITEM, Hannover, Germany. FAU - Schleh, Carsten AU - Schleh C FAU - Lauenstein, Hans-Dieter AU - Lauenstein HD FAU - Hussein, Riem AU - Hussein R FAU - Lubbers, Katrin AU - Lubbers K FAU - Pohlmann, Gerhard AU - Pohlmann G FAU - Switalla, Simone AU - Switalla S FAU - Sewald, Katherina AU - Sewald K FAU - Muller, Meike AU - Muller M FAU - Krug, Norbert AU - Krug N FAU - Muller-Goymann, Christel C AU - Muller-Goymann CC FAU - Braun, Armin AU - Braun A LA - eng PT - Journal Article PL - England TA - Inhal Toxicol JT - Inhalation toxicology JID - 8910739 RN - 0 (Drug Carriers) RN - 0 (Phospholipids) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Dose-Response Relationship, Drug MH - *Drug Carriers MH - Female MH - Humans MH - Image Processing, Computer-Assisted MH - Inhibitory Concentration 50 MH - L-Lactate Dehydrogenase/metabolism MH - Lung/*drug effects/pathology MH - Mice MH - Mice, Inbred BALB C MH - Microscopy, Confocal MH - Nanoparticles/*toxicity MH - Phospholipids/*toxicity MH - Risk Assessment MH - Tissue Culture Techniques MH - *Toxicity Tests EDAT- 2009/06/30 09:00 MHDA- 2010/02/02 06:00 CRDT- 2009/06/30 09:00 PHST- 2009/06/30 09:00 [entrez] PHST- 2009/06/30 09:00 [pubmed] PHST- 2010/02/02 06:00 [medline] AID - 10.1080/08958370903005769 [doi] PST - ppublish SO - Inhal Toxicol. 2009 Jul;21 Suppl 1:104-9. doi: 10.1080/08958370903005769.