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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...

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Autores principales: Cresti, Laura, Conte, Gemma, Cappello, Giovanni, Brunetti, Jlenia, Falciani, Chiara, Bracci, Luisa, Quaglia, Fabiana, Ungaro, Francesca, d’Angelo, Ivana, Pini, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863998/
https://www.ncbi.nlm.nih.gov/pubmed/36678633
http://dx.doi.org/10.3390/pharmaceutics15010003
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author Cresti, Laura
Conte, Gemma
Cappello, Giovanni
Brunetti, Jlenia
Falciani, Chiara
Bracci, Luisa
Quaglia, Fabiana
Ungaro, Francesca
d’Angelo, Ivana
Pini, Alessandro
author_facet Cresti, Laura
Conte, Gemma
Cappello, Giovanni
Brunetti, Jlenia
Falciani, Chiara
Bracci, Luisa
Quaglia, Fabiana
Ungaro, Francesca
d’Angelo, Ivana
Pini, Alessandro
author_sort Cresti, Laura
collection PubMed
description 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 Pseudomonas aeruginosa 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.
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spelling pubmed-98639982023-01-22 Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo Cresti, Laura Conte, Gemma Cappello, Giovanni Brunetti, Jlenia Falciani, Chiara Bracci, Luisa Quaglia, Fabiana Ungaro, Francesca d’Angelo, Ivana Pini, Alessandro Pharmaceutics Article 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 Pseudomonas aeruginosa 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. MDPI 2022-12-20 /pmc/articles/PMC9863998/ /pubmed/36678633 http://dx.doi.org/10.3390/pharmaceutics15010003 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cresti, Laura
Conte, Gemma
Cappello, Giovanni
Brunetti, Jlenia
Falciani, Chiara
Bracci, Luisa
Quaglia, Fabiana
Ungaro, Francesca
d’Angelo, Ivana
Pini, Alessandro
Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo
title Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo
title_full Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo
title_fullStr Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo
title_full_unstemmed Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo
title_short Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo
title_sort inhalable polymeric nanoparticles for pulmonary delivery of antimicrobial peptide set-m33: antibacterial activity and toxicity in vitro and in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863998/
https://www.ncbi.nlm.nih.gov/pubmed/36678633
http://dx.doi.org/10.3390/pharmaceutics15010003
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