title: Low cytotoxicity of solid lipid nanoparticles in in vitro and ex vivo lung models.
abstract: 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.
authors: Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM, Hannover, Germany.
authors: Matthias
authors: M
authors: Nassimi
authors: Carsten
authors: C
authors: Schleh
authors: Hans-Dieter
authors: HD
authors: Lauenstein
authors: Riem
authors: R
authors: Hussein
authors: Katrin
authors: K
authors: Lübbers
authors: Gerhard
authors: G
authors: Pohlmann
authors: Simone
authors: S
authors: Switalla
authors: Katherina
authors: K
authors: Sewald
authors: Meike
authors: M
authors: Müller
authors: Norbert
authors: N
authors: Krug
authors: Christel C
authors: CC
authors: Müller-Goymann
authors: Armin
authors: A
authors: Braun
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020128:Inhibitory Concentration 50; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000633:toxicity*; D010743:Phospholipids / Q000633:toxicity*; D018570:Risk Assessment; D046509:Tissue Culture Techniques; D018675:Toxicity Tests
chemical_list: D004337:Drug Carriers; D010743:Phospholipids; D007770:L-Lactate Dehydrogenase