Project Details
Projekt Print View

Designing nanoparticle-based inhaled antibiotics for the treatment of cystic fibrosis associated biofilms and infections and in vivo studies in a rat model.

Subject Area Pharmacy
Pneumology, Thoracic Surgery
Term from 2014 to 2020
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 256755002
 
During the first period, using systematic variations during the formulation process, we developed and optimized different micro- and nanoparticle formulations of polyester polymers in which different antibiotics with antipseudomonal activity were stably and efficiently encapsulated. The particles were extensively characterized regarding their physicochemical characteristics, and storage forms were developed. Using in vitro assays, we were able to demonstrate that non-encapsulated tobramycin exhibits no activity against biofilms of Pseudomonas aeruginosa and Burkholderia cepacia. By contrast, nanoparticle encapsulation restored the activity of tobramycin against these biofilms. The effectiveness of poly(D,L-lactide-co-glycolide)-poly[(D,L-lactide-co-glycolide)-co-polyethylene glycol] (PEG-PLGA)-encapsulated tobramycin against the biofilms was 1000-fold higher compared to that of the free drug or a blend of both components. The effective concentration of the encapsulated tobramycin was even lower than the concentrations measured during the tobramycin i.v. treatment. Moreover, the biofilms of B. cepacia, which is intrinsically resistant to tobramycin, could be efficiently eradicated. Both examples indicate an improved or even restored efficacy of the PEG-PLGA particles in vitro. The proposed project aims to transfer the in vitro results obtained during the first funding period to a rat model (chronic P. aeruginosa lung infection model) to investigate the safety and efficacy of the inhaled nanoparticle-encapsulated tobramycin in vivo. The aims are to (i) clarify the mechanism underlying the improved/restored efficacy of the encapsulated tobramycin, ii) formulate micro- and nanoparticles that are applicable for inhalation and confirm a sufficient pulmonary deposit of the drug, (iii) characterize the safety profile in vivo, and (iv) provide proof-of-concept of the superior efficacy of the inhaled tobramycin-encapsulated formulation compared to that of purely inhaled tobramycin.
DFG Programme Research Grants
 
 

Additional Information

Textvergrößerung und Kontrastanpassung