Disassembling bacterial extracellular matrix with DNase-coated nanoparticles to enhance antibiotic delivery in biofilm infections.
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.
Bacterial Infections and Antimicrobial Therapies, Institute for Bioengineering of Catalonia, Baldiri Reixac 15-21, 08028, Barcelona, Spain.
Aida
A
Baelo
Biomaterials for Regenerative Therapies, Institute for Bioengineering of Catalonia, Baldiri Reixac 15-21, 08028, Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
Riccardo
R
Levato
Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
Esther
E
Julián
Bacterial Infections and Antimicrobial Therapies, Institute for Bioengineering of Catalonia, Baldiri Reixac 15-21, 08028, Barcelona, Spain.
Anna
A
Crespo
Bacterial Infections and Antimicrobial Therapies, Institute for Bioengineering of Catalonia, Baldiri Reixac 15-21, 08028, Barcelona, Spain.
José
J
Astola
Infectious Diseases Research Laboratory, Infectious Diseases Department, Vall d'Hebron Research Institute VHIR, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Joan
J
Gavaldà
Biomaterials for Regenerative Therapies, Institute for Bioengineering of Catalonia, Baldiri Reixac 15-21, 08028, Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain; Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), Barcelona, Spain.
Elisabeth
E
Engel
Biomaterials for Regenerative Therapies, Institute for Bioengineering of Catalonia, Baldiri Reixac 15-21, 08028, Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
Miguel Angel
MA
Mateos-Timoneda
Bacterial Infections and Antimicrobial Therapies, Institute for Bioengineering of Catalonia, Baldiri Reixac 15-21, 08028, Barcelona, Spain. Electronic address: etorrents@ibecbarcelona.eu.
Eduard
E
Torrents
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy; D018441:Biofilms; D002460:Cell Line; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D003850:Deoxyribonuclease I / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D065546:Drug Liberation; D005109:Extracellular Matrix / Q000187:drug effects; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002939:Ciprofloxacin; D004247:DNA; D003850:Deoxyribonuclease I
Biofilm; Ciprofloxacin; DNase I; Nanoparticles; Pseudomonas aeruginosa