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Disassembling bacterial extracellular matrix with DNase-coated nanoparticles to enhance antibiotic delivery in biofilm infections

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10.1016/j.jconrel.2015.04.028
 
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Baelo, Aida
Levato, Riccardo
Julian, Esther
Crespo, A.
Astola, Jose
Gavalda, Joan
Engel López, ElisabethMés informacióMés informacióMés informació
Mateos Timoneda, Miguel ÁngelMés informació
Torrents, Eduard
CovenanteeHospital Universitari Vall d'Hebron
Document typeArticle
Defense date2015-07-10
Rights accessOpen Access
Attribution-NonCommercial-NoDerivs 3.0 Spain
Except where otherwise noted, content on this work is licensed under a Creative Commons license : Attribution-NonCommercial-NoDerivs 3.0 Spain
Abstract
Infections caused by biofilm-forming bacteria are a major threat to hospitalized patients and the main cause of chronic obstructive pulmonary disease and cystic fibrosis. There is an urgent necessity for novel therapeutic approaches, since current antibiotic delivery fails to eliminate biofilm-protected bacteria. In this study, ciprofloxacin-loaded poly(lactic-co-glycolic acid) nanoparticles, which were functionalized with DNase I, were fabricated using a green-solvent based method and their antibiofilm activity was assessed against Pseudomonas aeruginosa biofilms. Such nanoparticles constitute a paradigm shift in biofilm treatment, since, besides releasing ciprofloxacin in a controlled fashion, they are able to target and disassemble the biofilm by degrading the extracellular DNA that stabilize the biofilm matrix. These carriers were compared with free-soluble ciprofloxacin, and ciprofloxacin encapsulated in untreated and poly(lysine)-coated nanoparticles. DNase I-activated nanoparticles were not only able to prevent biofilm formation from planktonic bacteria, but they also successfully reduced established biofilm mass, size and living cell density, as observed in a dynamic environment in a flow cell biofilm assay. Moreover, repeated administration over three days of DNase I-coated nanoparticles encapsulating ciprofloxacin was able to reduce by 95% and then eradicate more than 99.8% of established biofilm, outperforming all the other nanoparticle formulations and the free-drug tested in this study. These promising results, together with minimal cytotoxicity as tested on J774 macrophages, allow obtaining novel antimicrobial nanoparticles, as well as provide clues to design the next generation of drug delivery devices to treat persistent bacterial infections. (C) 2015 Elsevier B.V. All rights reserved.
CitationBaelo, A., Levato, R., Julian, E., Crespo, A., Astola, J., Gavalda, J., Engel, E., Mateos, M., Torrents, E. Disassembling bacterial extracellular matrix with DNase-coated nanoparticles to enhance antibiotic delivery in biofilm infections. "Journal of controlled release", 10 Juliol 2015, vol. 209, p. 150-158. 
URIhttp://hdl.handle.net/2117/78233
DOI10.1016/j.jconrel.2015.04.028
ISSN0168-3659
Publisher versionhttp://www.sciencedirect.com/science/article/pii/S0168365915002588
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  • IBEC - Institute for Bioengineering of Catalonia - Articles de revista [50]
  • Departament de Ciència dels Materials i Enginyeria Metal·lúrgica - Articles de revista [961]
  • BBT - Grup de recerca en Biomaterials, Biomecànica i Enginyeria de Teixits - Articles de revista [405]
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