FFC#15/2017

Frog skin-derived peptides for treatment of Pseudomonas aeruginosa lung infection and bronchial epithelial repair: advanced in vitro and in vivo characterization and development of polymeric nanoparticles for lung delivery

FFC#15/2017

Frog skin-derived peptides for treatment of Pseudomonas aeruginosa lung infection and bronchial epithelial repair: advanced in vitro and in vivo characterization and development of polymeric nanoparticles for lung delivery

PRINCIPAL INVESTIGATOR

Maria Luisa Mangoni (Dipartimento di Scienze Biochimiche, Università La Sapienza)

Partner

Loretta Ferrera (U.O.C Genetica Medica, Istituto G. Gaslini, Genova)

RESEARCHERS

9

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

1 year

GOAL

€ 60.000 €

RESULTS

This project has carried out a multidisciplinary approach combining biochemical, microbiological techniques and preclinical testing in mouse models to explore the efficacy and safety profile of 1) the selected frog skin-derived peptide Esc(1-21) and in particular, its new designed diastereomer, 2) the peptide-loaded NPs(NanoParticles). Preclinical data in a murine model of P. aeruginosa lung infection have provided the first evidence of the success of polylactic-co-glycolic NPs as valuable nanocarriers to assist the delivery of antimicrobial peptides in the conductive airways as well as to boost up their antimicrobial effect. Furthermore, researchers have observed that the re-epithelialization of the bronchial epithelium by the selected peptides involves transactivation of epidermal growth factor receptor. On the basis of these findings, it can be concluded that the identified diastereomer of Esc (1-21) represents the best candidate for the development of inhalable nanoformulations These NPs could be further developed into dry powders for inhalation, allowing a much easier and faster administration as compared to nebulized liquid formulations or intravenous injection.


Congress abstracts

– Cappiello F, Carnicelli V, Angioi A et al. “Esc(1-21) and its diastereomer: antipseudomonal frog-skin derived peptides with multiple immunomodulatory properties” 16th Naples Workshop on Bioactive Peptides (June 7-9)
– Cappiello F, Carnicelli V, Angioi M et al. “The frog skin-derived peptides Esc(1-21) and its diastereomer: are they promoters of airway epithelium repair?” (Poster) XV FISV (Federazione Italiana Scienze della Vita) Congress, Sapienza University of Rome, Italy, September 18-21, 2018
– Cappiello F, Carnicelli V, Angioi M et al. “Esc(1-21) and its diastereomer: antipseudomonal frog-skin derived peptides with multiple immunomodulatory properties” 16th Naples Workshop on Bioactive Peptides, June 7-9, 2018 Naples
– Mangoni ML “How to control Pseudomonas aeruginosa-induced pneumonia? A lesson from derivatives of the amphibian skin peptide esculentin-1a” XV FISV (Federazione Italiana Scienze della Vita) Congress, Sapienza University of Rome, Italy, September 18-21, 2018
– Mangoni ML, Cappiello F, Casciano B et al. “How to control Pseudomonas aeruginosa-induced pneumonia and keratitis? A lesson from the amphibian skin-derived peptide Esculentin(1-21) and its diastereomer” 35th European Peptide Symposium, 26-31 August 2018, Dublin City University, Ireland

OTHER RESULTS

FFC #3/2024

Two molecules are effective in activating Heat Shock Proteins and enhancing the action of CFTR correctors with the F508del mutation in vitro.

FFC#5/2024

Some peptide nucleic acids (PNAs) re-sensitise Pseudomonas aeruginosa to the antibiotic meropenem in vitro and reduce its virulence.

FFC#1/2023

Tezacaftor, one of the components of Kaftrio, induces an accumulation of dihydroceramides both in vitro and in vivo in animal models