FFC#8/2023

Inhalable nanoparticles delivering peptidomimetic/antibiotic combinations for local treatment of CF lung infections

FFC#8/2023

Development of inhalable nanoparticles based on biopolymers to deliver antimicrobial molecules and antibiotics and enhance their antibacterial activity.

PRINCIPAL INVESTIGATOR

Eugenio Notomista (Dipartimento di Biologia Strutturale e Funzionale, Università Federico II, Napoli)

Partner

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

RESEARCHERS

11

CATEGORY

AREA 1 Therapies to correct the underlying defect

DURATION

2 years

GOAL

€ 136.500

RESULTS

The spread of antibiotic-resistant bacteria has focused attention on the need for new drugs to treat lung infections.
The main objective of this project was to develop inhalable nanoparticles that allow combinations of drugs, including antibiotics already in use (colistin and tobramycin) and P13#1, an antimicrobial molecule that replicates the behavior of peptides and proteins developed by researchers during the previous FFC#18/2018 project, to be administered directly to the lungs. 
The nanoparticles allow the molecules to be released directly into the mucus of the airways, maximizing their antimicrobial activity.

The study was conducted on pathogenic bacteria responsible for lung infection, mainly Pseudomonas aeruginosa and Staphylococcus aureus, grown both in free (planktonic) form and in biofilm form (a form of protective bacterial aggregation). 
The researchers produced nanoparticles consisting of two biocompatible and biodegradable polymers, called PLGA (polylactic-co-glycolic acid) and P407 (a molecule already approved for pharmaceutical use). 
The antibiotics colistin or tobramycin were then inserted into the nanoparticles obtained, and the chemical-physical properties (size, electrical charge, quantity and rate of antibiotic release, etc.) and biological activities (antimicrobial and antibiofilm activity) of the nanoparticles were studied.

The nanoparticles formed by PLGA+P407 proved particularly suitable for transporting tobramycin and colistin. Since these two antibiotics are widely used to treat respiratory tract infections, the nanoparticles developed during the project could be a very useful pharmaceutical tool in cystic fibrosis. In addition, P407 was found to greatly enhance the antimicrobial activity of colistin.

To transport the P13#1 molecule, different nanoparticles were produced from chitosan, a natural polymer with its own antimicrobial activity.

PLGA+P407 nanoparticles and colistin+P407 mixtures represent potential new treatments for lung infections in people with CF and will need to be further studied with in vivo experiments, in collaboration with the CFaCore service of FFC Ricerca.

In addition, chitosan nanoparticles are an interesting alternative to PLGA nanoparticles and could be used for the administration of mixtures that include P13#1.

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