Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases
In recent years, we have discovered Esc(1-21) and its diastereomer (Esc peptides) as valuable candidates for the treatment of Pseudomonas lung infection, especially in patients with cystic fibrosis (CF). Furthermore, engineered poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) were revealed to b...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/11/2297 |
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| author | Floriana Cappiello Bruno Casciaro Maria Rosa Loffredo Elena Puglisi Qiao Lin Dandan Yang Gemma Conte Ivana d’Angelo Francesca Ungaro Loretta Ferrera Raffaella Barbieri Laura Cresti Alessandro Pini Yuanpu Peter Di Maria Luisa Mangoni |
| author_facet | Floriana Cappiello Bruno Casciaro Maria Rosa Loffredo Elena Puglisi Qiao Lin Dandan Yang Gemma Conte Ivana d’Angelo Francesca Ungaro Loretta Ferrera Raffaella Barbieri Laura Cresti Alessandro Pini Yuanpu Peter Di Maria Luisa Mangoni |
| author_sort | Floriana Cappiello |
| collection | DOAJ |
| description | In recent years, we have discovered Esc(1-21) and its diastereomer (Esc peptides) as valuable candidates for the treatment of Pseudomonas lung infection, especially in patients with cystic fibrosis (CF). Furthermore, engineered poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) were revealed to be a promising pulmonary delivery system of antimicrobial peptides. However, the “ad hoc” development of novel therapeutics requires consideration of their stability, tolerability, and safety. Hence, by means of electrophysiology experiments and preclinical studies on healthy mice, we demonstrated that neither Esc peptides or Esc-peptide-loaded PLGA NPs significantly affect the integrity of the lung epithelium, nor change the global gene expression profile of lungs of treated animals compared to those of vehicle-treated animals. Noteworthy, the Esc diastereomer endowed with the highest antimicrobial activity did not provoke any pulmonary pro-inflammatory response, even at a concentration 15-fold higher than the efficacy dosage 24 h after administration in the free or encapsulated form. The therapeutic index was ≥70, and the peptide was found to remain available in the bronchoalveolar lavage of mice, after two days of incubation. Overall, these studies should open an avenue for a new up-and-coming pharmacological approach, likely based on inhalable peptide-loaded NPs, to address CF lung disease. |
| first_indexed | 2024-03-09T18:45:24Z |
| format | Article |
| id | doaj.art-c752e81a72934da5aa7c65a8c4dfde39 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T18:45:24Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c752e81a72934da5aa7c65a8c4dfde392023-11-24T06:19:53ZengMDPI AGPharmaceutics1999-49232022-10-011411229710.3390/pharmaceutics14112297Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious DiseasesFloriana Cappiello0Bruno Casciaro1Maria Rosa Loffredo2Elena Puglisi3Qiao Lin4Dandan Yang5Gemma Conte6Ivana d’Angelo7Francesca Ungaro8Loretta Ferrera9Raffaella Barbieri10Laura Cresti11Alessandro Pini12Yuanpu Peter Di13Maria Luisa Mangoni14Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Pharmacy, University of Napoli Federico II, 80131 Napoli, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), University of Campania Luigi Vanvitelli, 81100 Caserta, ItalyDepartment of Pharmacy, University of Napoli Federico II, 80131 Napoli, ItalyU.O.C. Genetica Medica, IRCCS, Istituto Giannina Gaslini, 16147 Genoa, ItalyBiophysic Institute, Consiglio Nazionale delle Ricerche (CNR), 16149 Genoa, ItalyDepartment of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyDepartment of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyIn recent years, we have discovered Esc(1-21) and its diastereomer (Esc peptides) as valuable candidates for the treatment of Pseudomonas lung infection, especially in patients with cystic fibrosis (CF). Furthermore, engineered poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) were revealed to be a promising pulmonary delivery system of antimicrobial peptides. However, the “ad hoc” development of novel therapeutics requires consideration of their stability, tolerability, and safety. Hence, by means of electrophysiology experiments and preclinical studies on healthy mice, we demonstrated that neither Esc peptides or Esc-peptide-loaded PLGA NPs significantly affect the integrity of the lung epithelium, nor change the global gene expression profile of lungs of treated animals compared to those of vehicle-treated animals. Noteworthy, the Esc diastereomer endowed with the highest antimicrobial activity did not provoke any pulmonary pro-inflammatory response, even at a concentration 15-fold higher than the efficacy dosage 24 h after administration in the free or encapsulated form. The therapeutic index was ≥70, and the peptide was found to remain available in the bronchoalveolar lavage of mice, after two days of incubation. Overall, these studies should open an avenue for a new up-and-coming pharmacological approach, likely based on inhalable peptide-loaded NPs, to address CF lung disease.https://www.mdpi.com/1999-4923/14/11/2297antimicrobial peptidescystic fibrosislung infectionbiodegradable nanocarriertherapeutic indextransepithelial resistance |
| spellingShingle | Floriana Cappiello Bruno Casciaro Maria Rosa Loffredo Elena Puglisi Qiao Lin Dandan Yang Gemma Conte Ivana d’Angelo Francesca Ungaro Loretta Ferrera Raffaella Barbieri Laura Cresti Alessandro Pini Yuanpu Peter Di Maria Luisa Mangoni Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases Pharmaceutics antimicrobial peptides cystic fibrosis lung infection biodegradable nanocarrier therapeutic index transepithelial resistance |
| title | Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases |
| title_full | Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases |
| title_fullStr | Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases |
| title_full_unstemmed | Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases |
| title_short | Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases |
| title_sort | pulmonary safety profile of esc peptides and esc peptide loaded poly lactide co glycolide nanoparticles a promising therapeutic approach for local treatment of lung infectious diseases |
| topic | antimicrobial peptides cystic fibrosis lung infection biodegradable nanocarrier therapeutic index transepithelial resistance |
| url | https://www.mdpi.com/1999-4923/14/11/2297 |
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