Infections caused by these bacteria are a major threat to hospitalized patients, in medical implants and in chronic wounds, as well as being the main cause of chronic obstructive pulmonary disease (COPD) and cystic fibrosis.
Surface plot analysis of Pseudomonas aeruginosa wild type PAO1 four-day old biofilm. Close images of the biofilm under the confocal scanning laser microscopy. It is shown a representation of the nanoparticles used in this study.
In the study, which involved IBEC’s Biomaterials for Regenerative Therapies and Bacterial Infections: Antimicrobial Therapies groups, together with the Autonomous University of Barcelona and the Vall d’Hebron Research Institute, poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the antibiotic ciprofloxacin which had been functionalized with DNase I, a nuclease that digests DNA, were fabricated. They were then tested for antibiofilm activity against biofilms of P. aeruginosa, a bacterium that’s often the cause of lung problems in cystic fibrosis patients, and their results compared favorably with those of free-soluble ciprofloxacin, and ciprofloxacin encapsulated in untreated and poly(lysine)-coated nanoparticles.
“There is an urgent necessity for new therapeutic approaches for infections caused by biofilm-forming bacteria, since current antibiotics fail to eliminate these types of bacteria,” explains Eduard Torrents, head of the Bacterial Infections: Antimicrobial Therapies group. “Our nanoparticle strategy constitutes a paradigm shift in biofilm treatment, as besides releasing ciprofloxacin in a controlled fashion, they are able to target and disassemble the biofilm by degrading the extracellular DNA that stabilizes its matrix.”
The promising results, taken together with the minimal cytotoxicity of the new nanoparticles, open new avenues towards eradicating established bacterial biofilms by modifying the surface of the nanoparticles and thus tailoring them to target specific bacterial infections.
Reference article: Aida Baelo, Ricardo Levato, Esther Julián, Anna Crespo, José Astola, Joan Gavaldá, Elisabeth Engel, Miguel Angel Mateos-Timoneda, Eduard Torrents (2015). “Disassembling bacterial extracellular matrix with DNase-coated nanoparticles to enhance antibiotic delivery in biofilm infections”. Journal of Controlled Release, 209, p150–158