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

JOURNAL OF CONTROLLED RELEASE

卷:209

Article

Baelo, Aida¹  Levato, Riccardo^2,3  Julian, Esther⁴  Crespo, Anna¹  Astola, Jose¹  Gavalda, Joan⁵  Engel, Elisabeth^2,3,6  Angel Mateos-Timoneda, Miguel^2,3  Torrents, Eduard¹ 

[1] Inst Bioengn Catalonia, Bacterial Infect & Antimicrobial Therapies, Barcelona 08028, Spain

[2] Inst Bioengn Catalonia, Biomat Regenerat Therapies, Barcelona 08028, Spain

[3] CIBER Bioingn Biomat & Nanomed, Barcelona, Spain

[4] Univ Autonoma Barcelona, Fac Biociencies, Dept Genet & Microbiol, Bellaterra 08193, Spain

[5] Hosp Univ Vall dHebron, Vall dHebron Res Inst VHIR, Dept Infect Dis, Infect Dis Res Lab, Barcelona, Spain

[6] Tech Univ Catalonia UPC, Dept Mat Sci & Met, Barcelona, Spain

关键词: Pseudomonas aeruginosa;    Biofilm;    Ciprofloxacin;    DNase I;    Nanoparticles;   

DOI  :  10.1016/j.jconrel.2015.04.028

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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