title: Improved effect of amikacin-loaded poly(D,L-lactide-co-glycolide) nanoparticles against planktonic and biofilm cells of Pseudomonas aeruginosa.
abstract: OBJECTIVE
  Amikacin is one of the most effective antibiotics against Pseudomonas aeruginosa infections, but because of its high toxicity, the use of this antibiotic has been clinically limited. In the present study, amikacin was successfully loaded into a new formulation of nanoparticles (NPs) based on poly(d,l-lactide-co-glycolide) 50 : 50 in order to enhance the treatment efficacy. The synthetized amikacin-loaded PLGA nanoparticles with high drug loading and stability were used to eliminate P. aeruginosa cells in planktonic and biofilm states.
  
  
  METHODS
  P. aeruginosa PAO1 biofilm susceptibility studies were done using the minimum biofilm eradication concentration assay. The association of fluorescently labeled amikacin-loaded nanoparticles (A-NPs) with mouse monocyte macrophage cells (RAW 264.7), and the nanoparticles ability to interact and eradicate the bacterial cells even in the form of biofilms, was investigated using Flow cytometric studies and confocal laser scanning microscopy.
  
  
  RESULTS
  Flow cytometric studies showed that these NPs were able to interact with planktonic and biofilm bacterial cells. Moreover, following 1 h of incubation of A-NPs with 1-day-old biofilm, it was found that particles penetrate through the entire biofilm thickness. Live/dead fluorescent staining followed by CLSM analysis showed that the A-NPs were more effective than free drug in biofilm eradication.
  
  
  CONCLUSIONS
  The good antibacterial and antibiofilm activities of A-NPs, in addition to their ability to enter macrophages without any cytotoxicity for these cells, make them a potential candidate to treat P. aeruginosa infections.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain.|Department of Microbiology and Parasitology, University of Navarra, Pamplona, Spain.|Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Sabaeifard
authors.affiliation: Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.
authors.forename: Ahya
authors.initials: A
authors.lastname: Abdi-Ali
authors.affiliation: Department of Microbiology and Parasitology, University of Navarra, Pamplona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gamazo
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Irache
authors.affiliation: Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Soudi
mesh_terms: D000583:Amikacin / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D000067996:RAW 264.7 Cells
chemical_list: D000900:Anti-Bacterial Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000583:Amikacin