In vitro inhalation cytotoxicity testing of therapeutic nanosystems for pulmonary infection

Autor: Ritter, Detlef, Knebel, Jan, Niehof, Monika, Loinaz, Iraida, Marradi, Marco, Gracia, Raquel, Te Welscher, Yvonne, van Nostrum, Cornelus F., Falciani, Chiara, Pini, Alessandro, Strandh, Magnus, Hansen, Tanja, Afd Pharmaceutics, Pharmaceutics
Přispěvatelé: Afd Pharmaceutics, Pharmaceutics, Publica
Rok vydání: 2019
Předmět:
0301 basic medicine
Lung Diseases
aerosol
endogenous compound
Inhalation Toxicology
animal cell
Pharmacology
0302 clinical medicine
Nanosystems
Lung
Micelles
polypeptide antibiotic agent
Liposome
Inhalation
lung infection
Chemistry
nanoparticle
article
General Medicine
Bacterial Infections
respiratory system
Air-liquid interface
Antimicrobial peptides
In vitro
Pulmonary infection
Toxicity
Anti-Bacterial Agents
030220 oncology & carcinogenesis
polymerization
liposome
cytotoxicity
Methacrylates
toxicology
in vitro study
Cell Survival
animal experiment
in vivo study
lactose
03 medical and health sciences
Route of administration
In vivo
micelle
Humans
controlled study
lung toxicity
Aerosols
nonhuman
animal model
lung cell line
prediction
Bioavailability
respiratory tract diseases
Nylons
030104 developmental biology
A549 Cells
Liposomes
Nanoparticles
Nanocarriers
bioavailability
Peptides
Zdroj: Toxicology in Vitro, 63. NLM (Medline)
ISSN: 1879-3177
0887-2333
Popis: 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.
Databáze: OpenAIRE
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