In vitro inhalation cytotoxicity testing of therapeutic nanosystems for pulmonary infection.
Due to the increasing need of new treatment options against bacterial lung infections, novel antimicrobial peptides (AMPs) are under development. Local bioavailability and less systemic exposure lead to the inhalation route of administration. Combining AMPs with nanocarriers (NCs) into nanosystems (NSs) might be a technique for improved results. An air-liquid interface (ALI) in vitro inhalation model was set up including a human alveolar lung cell line (A549) and an optimized exposure system (P.R.I.T.® ExpoCube®) to predict acute local lung toxicity. The approach including aerosol controls (cupper-II-sulfate and lactose) delivered lowest observable adverse effect levels (LOAELs). Different combinations of AMPs (AA139, M33) and NCs (polymeric nanoparticles (PNPs), micelles and liposomes) were tested under ALI and submerged in vitro conditions. Depending on the nature of AMP and NCs, packing of AMPs into NSs reduced the AMP-related toxicity. Large differences were found between the LOAELs determined by submerged or ALI testing with the ALI approach indicating higher sensitivity of the ALI model. Since aerosol droplet exposure is in vivo relevant, it is assumed that ALI based results represents the more significant source than submerged testing for in vivo prediction of local acute lung toxicity. In accordance with the current state-of-the-art view, this study shows that ALI in vitro inhalation models are promising tools to further develop in vitro methods in the field of inhalation toxicology.
['Ritter|Detlef|D|', 'Knebel|Jan|J|', 'Niehof|Monika|M|', 'Loinaz|Iraida|I|', 'Marradi|Marco|M|', 'Gracia|Raquel|R|', 'Te Welscher|Yvonne|Y|', 'van Nostrum|Cornelus F|CF|', 'Falciani|Chiara|C|', 'Pini|Alessandro|A|', 'Strandh|Magnus|M|', 'Hansen|Tanja|T|']
D000072283:A549 Cells D000336:Aerosols D000900:Anti-Bacterial Agents D001424:Bacterial Infections D002470:Cell Survival D006801:Humans D008081:Liposomes D008168:Lung D008171:Lung Diseases D008689:Methacrylates D008823:Micelles D053758:Nanoparticles D009757:Nylons D010455:Peptides
In vitro Inhalation Nanosystems Pulmonary infection Antimicrobial peptides Air-liquid interface Toxicity