Nanoparticulate Drug Delivery Systems for Pseudomonas aeruginosa Infected Lungs in Cystic Fibrosis

Current pulmonary treatments against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation and immobilization of the drug in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance.

The present work suggests pulmonary antibiotic delivery with high load, capable of penetrating the tight mesh of biofilm/mucus as a solution to existing treatment bottlenecks. The potential use of nanoparticulate drug delivery systems to improve the treatment efficiency of lung infections in CF lungs is investigated.

First chapter describes counter-ion complexes as a strategy to enhance drug load and demonstrates its applicability to different antibiotic classes, as well as counter-ions. The second chapter focuses on the drug delivery system development and its optimization via design-of-experiments approach. For the proof-of-concept studies, biodegradable and biocompatible poly (lactic-co-glycolic acid) was suggested and ciprofloxacin was used as model drug substance. MicroJet Reactor (MJR) technology, a precise preparation technique performed under controlled conditions, was employed. Effect of each process parameter was evaluated to ensure quality-by-design. Final chapter is dedicated to physico-chemical and in vitro characterization of the optimized nanoparticles.

Overall, the new established approach offers counter-ion complex loaded PLGA NPs as promising pulmonary nano drug delivery system against P. aeruginosa infections in CF lung.

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