Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo

Development of inhalable formulations for delivering peptides to the conductive airways and shielding their interactions with airway barriers, thus enhancing peptide/bacteria interactions, is an important part of peptide-based drug development for lung applications. Here, we report the construction...

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutics 2022-12, Vol.15 (1), p.3
Main Authors: Cresti, Laura, Conte, Gemma, Cappello, Giovanni, Brunetti, Jlenia, Falciani, Chiara, Bracci, Luisa, Quaglia, Fabiana, Ungaro, Francesca, d'Angelo, Ivana, Pini, Alessandro
Format: Article
Language:English
Subjects:
aerosolization
Antibiotics
Antimicrobial agents
Bacteria
Biofilms
Chromatography
Cystic fibrosis
Infections
inhalable formulations
lung delivery
Mass spectrometry
Molecular weight
nanoparticle properties
nanoparticle/mucus interactions
Nanoparticles
Peptides
Polyethylene glycol
polymeric nanoparticles
Scientific imaging
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Development of inhalable formulations for delivering peptides to the conductive airways and shielding their interactions with airway barriers, thus enhancing peptide/bacteria interactions, is an important part of peptide-based drug development for lung applications. Here, we report the construction of a biocompatible nanosystem where the antimicrobial peptide SET-M33 is encapsulated within polymeric nanoparticles of poly(lactide-co-glycolide) (PLGA) conjugated with polyethylene glycol (PEG). This system was conceived for better delivery of the peptide to the lungs by aerosol. The encapsulated peptide showed prolonged antibacterial activity, due to its controlled release, and much lower toxicity than the free molecule. The peptide-based nanosystem killed in planktonic and sessile forms in a dose-dependent manner, remaining active up to 72 h after application. The encapsulated peptide showed no cytotoxicity when incubated with human bronchial epithelial cells from healthy individuals and from cystic fibrosis patients, unlike the free peptide, which showed an EC50 of about 22 µM. In vivo acute toxicity studies in experimental animals showed that the peptide nanosystem did not cause any appreciable side effects, and confirmed its ability to mitigate the toxic and lethal effects of free SET-M33.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15010003