Antimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Pseudomonas aeruginosa Infections
Chiara Falciani, 1 Fabrizia Zevolini, 1 Jlenia Brunetti, 1 Giulia Riolo, 2 Raquel Gracia, 3 Marco Marradi, 3 Iraida Loinaz, 3 Christina Ziemann, 4 Unai Cossío, 5 Jordi Llop, 5, 6 Luisa Bracci, 1 Alessandro Pini 1 1Department of Medical Biotechnologies, University of Siena, Siena, Italy;...
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Dove Medical Press
2020
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oai:doaj.org-article:f56de498c51e4136a60fb4979116a6332021-12-02T03:36:31ZAntimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Pseudomonas aeruginosa Infections1178-2013https://doaj.org/article/f56de498c51e4136a60fb4979116a6332020-02-01T00:00:00Zhttps://www.dovepress.com/antimicrobial-peptide-loaded-nanoparticles-as-inhalation-therapy-for-p-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Chiara Falciani, 1 Fabrizia Zevolini, 1 Jlenia Brunetti, 1 Giulia Riolo, 2 Raquel Gracia, 3 Marco Marradi, 3 Iraida Loinaz, 3 Christina Ziemann, 4 Unai Cossío, 5 Jordi Llop, 5, 6 Luisa Bracci, 1 Alessandro Pini 1 1Department of Medical Biotechnologies, University of Siena, Siena, Italy; 2Setlance, Siena, Italy; 3CIDETEC, Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián, Spain; 4Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany; 5CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), San Sebastian, Spain; 6Centro de Investigación Biomédica en red Enfermedades Respiratorias – CIBERES, Madrid, SpainCorrespondence: Chiara FalcianiDepartment of Medical Biotechnologies, University of Siena, via Aldo Moro 2, Siena, ItalyTel +39 0577 232022Email chiara.falciani@unisi.itIntroduction: Antibiotic-resistant bacteria kill 25,000 people every year in the EU. Patients subject to recurrent lung infections are the most vulnerable to severe or even lethal infections. For these patients, pulmonary delivery of antibiotics would be advantageous, since inhalation can achieve higher concentration in the lungs than iv administration and can provide a faster onset of action. This would allow for the delivery of higher doses and hence reduce the number of treatments required. We report here about a new nanosystem (M33-NS) obtained by capturing SET-M33 peptide on single-chain dextran nanoparticles. SET-M33 is a non-natural antimicrobial peptide synthesized in branched form. This form gives the peptide resistance to degradation in biological fluids. SET-M33 has previously shown efficacy in vitro against about one hundred of Gram-negative multidrug and extensively drug-resistant clinical isolates and was also active in preclinical infection models of pneumonia, sepsis and skin infections.Methods: The new nanosystem was evaluated for its efficacy in bacteria cells and in a mouse model of pneumonia. Toxicity and genotoxicity were also tested in vitro. Biodistribution and pharmacokinetic studies in healthy rats were carried out using a radiolabeled derivative of the nanosystem.Results: The M33-nanosystem, studied here, showed to be effective against Pseudomonas aeruginosa in time-kill kinetic experiments. Cytotoxicity towards different animal cell lines was acceptable. Lung residence time of the antimicrobial peptide, administered via aerosol in healthy rats, was markedly improved by capturing SET-M33 on dextran nanoparticles. M33-NS was also efficient in eradicating pulmonary infection in a BALB/c mouse model of pneumonia caused by P. aeruginosa.Discussion: This study revealed that the encapsulation of the antimicrobial peptide in dextran nanoparticles markedly improved lung residence time of the peptide administered via aerosol. The result has to be considered among the aims of the development of a new therapeutic option for patients suffering recurrent infections, that will benefit from high local doses of persistent antimicrobials.Keywords: antimicrobial peptides, nanoparticles, multi-drug resistanceFalciani CZevolini FBrunetti JRiolo GGracia RMarradi MLoinaz IZiemann CCossío ULlop JBracci LPini ADove Medical Pressarticleantimicrobial peptidesnanoparticlesmulti-drug resistance.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 1117-1128 (2020) |
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antimicrobial peptides nanoparticles multi-drug resistance. Medicine (General) R5-920 |
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antimicrobial peptides nanoparticles multi-drug resistance. Medicine (General) R5-920 Falciani C Zevolini F Brunetti J Riolo G Gracia R Marradi M Loinaz I Ziemann C Cossío U Llop J Bracci L Pini A Antimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Pseudomonas aeruginosa Infections |
| description |
Chiara Falciani, 1 Fabrizia Zevolini, 1 Jlenia Brunetti, 1 Giulia Riolo, 2 Raquel Gracia, 3 Marco Marradi, 3 Iraida Loinaz, 3 Christina Ziemann, 4 Unai Cossío, 5 Jordi Llop, 5, 6 Luisa Bracci, 1 Alessandro Pini 1 1Department of Medical Biotechnologies, University of Siena, Siena, Italy; 2Setlance, Siena, Italy; 3CIDETEC, Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián, Spain; 4Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany; 5CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), San Sebastian, Spain; 6Centro de Investigación Biomédica en red Enfermedades Respiratorias – CIBERES, Madrid, SpainCorrespondence: Chiara FalcianiDepartment of Medical Biotechnologies, University of Siena, via Aldo Moro 2, Siena, ItalyTel +39 0577 232022Email chiara.falciani@unisi.itIntroduction: Antibiotic-resistant bacteria kill 25,000 people every year in the EU. Patients subject to recurrent lung infections are the most vulnerable to severe or even lethal infections. For these patients, pulmonary delivery of antibiotics would be advantageous, since inhalation can achieve higher concentration in the lungs than iv administration and can provide a faster onset of action. This would allow for the delivery of higher doses and hence reduce the number of treatments required. We report here about a new nanosystem (M33-NS) obtained by capturing SET-M33 peptide on single-chain dextran nanoparticles. SET-M33 is a non-natural antimicrobial peptide synthesized in branched form. This form gives the peptide resistance to degradation in biological fluids. SET-M33 has previously shown efficacy in vitro against about one hundred of Gram-negative multidrug and extensively drug-resistant clinical isolates and was also active in preclinical infection models of pneumonia, sepsis and skin infections.Methods: The new nanosystem was evaluated for its efficacy in bacteria cells and in a mouse model of pneumonia. Toxicity and genotoxicity were also tested in vitro. Biodistribution and pharmacokinetic studies in healthy rats were carried out using a radiolabeled derivative of the nanosystem.Results: The M33-nanosystem, studied here, showed to be effective against Pseudomonas aeruginosa in time-kill kinetic experiments. Cytotoxicity towards different animal cell lines was acceptable. Lung residence time of the antimicrobial peptide, administered via aerosol in healthy rats, was markedly improved by capturing SET-M33 on dextran nanoparticles. M33-NS was also efficient in eradicating pulmonary infection in a BALB/c mouse model of pneumonia caused by P. aeruginosa.Discussion: This study revealed that the encapsulation of the antimicrobial peptide in dextran nanoparticles markedly improved lung residence time of the peptide administered via aerosol. The result has to be considered among the aims of the development of a new therapeutic option for patients suffering recurrent infections, that will benefit from high local doses of persistent antimicrobials.Keywords: antimicrobial peptides, nanoparticles, multi-drug resistance |
| format |
article |
| author |
Falciani C Zevolini F Brunetti J Riolo G Gracia R Marradi M Loinaz I Ziemann C Cossío U Llop J Bracci L Pini A |
| author_facet |
Falciani C Zevolini F Brunetti J Riolo G Gracia R Marradi M Loinaz I Ziemann C Cossío U Llop J Bracci L Pini A |
| author_sort |
Falciani C |
| title |
Antimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Pseudomonas aeruginosa Infections |
| title_short |
Antimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Pseudomonas aeruginosa Infections |
| title_full |
Antimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Pseudomonas aeruginosa Infections |
| title_fullStr |
Antimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Pseudomonas aeruginosa Infections |
| title_full_unstemmed |
Antimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Pseudomonas aeruginosa Infections |
| title_sort |
antimicrobial peptide-loaded nanoparticles as inhalation therapy for pseudomonas aeruginosa infections |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/f56de498c51e4136a60fb4979116a633 |
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