FFC#17/2016

Development of inhalable particles for optimal delivery of a potent antimicrobial molecule in Pseudomonas aeruginosa infected lungs

FFC#17/2016

Development of inhalable particles for optimal delivery of a potent antimicrobial molecule in Pseudomonas aeruginosa infected lungs

PRINCIPAL INVESTIGATOR

Alessandro Pini (Dipartimento di Biotecnologia Medica, Università di Siena)

Partner

Ivana d’Angelo (Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Di.S.T.A.Bi.F., Seconda Università di Napoli)

RESEARCHERS

8

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

2 years

GOAL

€ 50.000 €

RESULTS

The M33 peptide was produced according to the manufacturing procedures previously developed in the and encapsulated in different polymeric NP formulations, in order to achieve an optimized peptide formulation able to improve the M33 activity. The developed M33-loaded NP formulations were tested in vitro for their efficacy and toxicity. During the project, several lots of PLGA-based nanoparticles (NPs) containing M33 were produced. The obtained delivery systems showed optimized size, zeta potential, in vitro aerosolization properties and peptide encapsulation and in vitro release. The obtained formulations were tested for antimicrobial activity by MIC assays against P. aeruginosa, and for toxicity against eukaryotic cells. No significant toxicity was revealed. In parallel, an animal model of lung infection with P. aeruginosa was set up using a Penn Century device for nebulization and an aerosol machine specifically constructed for animal exposure to encapsulated M33. The effectiveness of the formulations has to be further analyzed in the future.


Pubblications

– Puglia M, Landi C, Gagliardi A et al. “The proteome speciation of an immortalized cystic fibrosis cell line: New perspectives on the pathophysiology of the disease” Journal of Proteomics 2018 Jan 6;170:28-42

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