In vitro inhalation cytotoxicity testing of therapeutic nanosystems for pulmonary infection

Detlef Ritter, Jan Knebel, Monika Niehof, Iraida Loinaz, Marco Marradi, Raquel Gracia, Yvonne Te Welscher, Cornelus F. van Nostrum, Chiara Falciani, Alessandro Pini, Magnus Strandh, Tanja Hansen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Article number104714
Number of pages11
JournalToxicology in Vitro
Volume63
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Air-liquid interface
  • Antimicrobial peptides
  • In vitro
  • Inhalation
  • Nanosystems
  • Pulmonary infection
  • Toxicity
  • aerosol
  • animal cell
  • animal experiment
  • animal model
  • article
  • bioavailability
  • controlled study
  • cytotoxicity
  • in vitro study
  • in vivo study
  • lung cell line
  • lung infection
  • lung toxicity
  • micelle
  • nonhuman
  • polymerization
  • prediction
  • toxicology
  • endogenous compound
  • lactose
  • liposome
  • nanoparticle
  • polypeptide antibiotic agent

Fingerprint

Dive into the research topics of 'In vitro inhalation cytotoxicity testing of therapeutic nanosystems for pulmonary infection'. Together they form a unique fingerprint.

Cite this