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Cytotoxicity testing of therapeutic nanosystems for pulmonary infection using an air-lifted interphase in-vitro test system

: Knebel, Jan W.; Ritter, Detlef; Niehof, Monika; Hansen, Tanja; Strandh, M.; Falciani, C.; Flores, M.; Welscher, Y. te; Nostrum, C. van; Gracia, R.; Marradi, M.; Loinaz, I.


Toxicology letters 295 (2018), Supplement 1, S.S69
ISSN: 0378-4274
ISSN: 1879-3169
European Societies of Toxicology (EUROTOX Congress) <54, 2018, Brussels>
Fraunhofer ITEM ()

While searching for effective antibiotics against resistant bacteria, nanocompounds are developed today, which may serve as drug carriers for the antibiotic active substances. In the case of respiratory infections, the administration of such combined antibiotic nanosystems (NS) via the inhalation route is the first choice in order to combat the bacteria directly at the site of action. Here we report about the in vitro investigation on the cytotoxic effects of 4 nanosystems and a free antimicrobial peptide (AMP) on a human lung cell line (A549) in a realistic test environment. Test substances as well as vehicle, positive (CuSO4) and negative (Lactose) controls were aerosolized. Cells, grown on membranes at the air-liquid interphase, were exposed to the airborne test and reference substances using the P.R.I.T.® ALI technology. After exposure, cells were postincubated for 24 hrs before cellular viability was determined by use of the tetrazolium salt conversion assay (WST-1). The results indicated that the exposure scenario had no adverse effect on the cells as revealed by the vehicle controls. CuSO4, known as a mild human lung toxicant, led to a clear dose-effect relationship, whereas increasing concentrations of lactose showed no cytotoxic effect. The free antimicrobial peptide displayed the strongest toxicity of all test substances and revealed more toxic potency than the positive control (CuSO4). The comparison on dosage based grouping between the free AMP and the nanosystem, tested at the same relative antibiotics concentration, revealed that packing into a micelle nanosystem significantly reduced the toxicity of the AMP. When comparing the effect of the four NS at the highest dosage the results show, that NS #2 had a significantly higher impact on the cell viability than the other three nanosystems. Therefore it is concluded that the protective effects of the nanosystems were dependent on the antibiotic/nanocompound combination. EU grant agreement No 604434.