Julia Ernst
Friedrich Schiller University Jena, Germany
Title: Polymeric micro- and nanocarriers for the treatment of biofilm-associated infections in cystic fibrosis
Biography
Biography: Julia Ernst
Abstract
Antimicrobial treatment is a cornerstone of cystic fibrosis (CF) therapy, as approximately 90% of CF patients die from lung destruction promoted by pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia. However, the efficacy of the inhaled antibiotics is limited due to a hindered penetration of drugs through mucus and bacterial biofilms which is difficult to imitate in vitro. In our experiments we developed a way to overcome these barriers, by loading tobramycin (Tb) into biodegradable poly(lactic-co glycolic acid) based nano- (NP) and microparticles (MP) modified with PEG and a blue fluorescent dye (AMCA) to investigate the penetration in mucus and the antibiotic efficacy in bacterial biofilms. Tb-loaded particles of 830 nm (MP) or 230 nm (NP) and zeta potentials of ca. -10 mV were prepared by a double-emulsion evaporation method and characterized by SEM and HPLC. For biofilm experiments, bacteria were cultivated in artificial mucus (AM)-containing chamber slides to allow the formation of a biofilm close to those of CF patients or in a microfluidic device to imitate the physiological shear flow in the body. The excellent penetration abilities of Tb-loaded particles through AM and biofilms and the remarkable antimicrobial efficacy in comparison to the free drug was confirmed by confocal laser scanning microscopy of LIVE/DEAD® stained biofilms. In conclusion, we demonstrated that the NP and MP displayed excellent properties as biocompatible, mucus-penetrating delivery systems for antibiotics with improved deposition and bacterial killing of biofilm-embedded pathogens even under more physiological conditions compared to conventional in vitro models.