Low cytotoxicity of solid lipid nanoparticles in in vitro and ex vivo lung models.
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.
Nassimi
Matthias
M
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM, Hannover, Germany.
Schleh
Carsten
C
Lauenstein
Hans-Dieter
HD
Hussein
Riem
R
Lübbers
Katrin
K
Pohlmann
Gerhard
G
Switalla
Simone
S
Sewald
Katherina
K
Müller
Meike
M
Krug
Norbert
N
Müller-Goymann
Christel C
CC
Braun
Armin
A
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
D004337:Drug Carriers; D010743:Phospholipids; D007770:L-Lactate Dehydrogenase