title: Gentamicin-loaded microspheres for reducing the intracellular Brucella abortus load in infected monocytes.
abstract: OBJECTIVE
  The intracellular antibiotic efficiency of gentamicin-loaded microspheres in the context of Brucella-infected murine monocytes was examined in vitro with a view to developing improved therapies for the treatment of brucellosis.
  
  
  METHODS
  Biodegradable microspheres made of end-group capped and uncapped poly(lactide-co-glycolide) 50:50 (PLGA 50:50 and PLGA 50:50H) and containing gentamicin sulphate were used to target Brucella abortus-infected J774 monocyte-macrophages. The infected cells were treated with 15 micro g of free or microencapsulated gentamicin and the efficacy of the treatments was measured after 24 h.
  
  
  RESULTS
  The particle sizes were below 8 micro m and in vitro release of gentamicin from the microspheres followed a continuous (PLGA 50:50H) or a multiphasic (PLGA 50:50) pattern over 50 days. Treatment with gentamicin microencapsulated into the end-group uncapped PLGA 50:50H microspheres, decreased significantly the number of intracellular bacteria (typically by 2 log(10)) in comparison with untreated infected cells. Addition of 2% poloxamer 188 to the microsphere dispersion medium further reduced the infection (3.5 log(10)). Opsonization of the particles with non-immune mouse serum had no effect on the antibacterial efficacy of the microspheres. End-group capped PLGA 50:50 type microspheres containing the antibiotic were less effective at reducing intracellular bacteria ( approximately 1 log(10) reduction), although addition of poloxamer 188 to the dispersion medium again enhanced their intracellular antibacterial activity. Placebo PLGA 50:50 and PLGA 50:50H microspheres had no bactericidal activity.
  
  
  CONCLUSIONS
  The results indicate that PLGA 50:50-microencapsulated gentamicin sulphate may be suitable for efficient drug targeting and delivery to reduce intracellular Brucella infections.
authors.affiliation: Department of Microbiology, University of Navarra, 31008 Pamplona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Prior
authors.forename: Bruno
authors.initials: B
authors.lastname: Gander
authors.forename: Concepción
authors.initials: C
authors.lastname: Lecároz
authors.forename: Juan M
authors.initials: JM
authors.lastname: Irache
authors.forename: Carlos
authors.initials: C
authors.lastname: Gamazo
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002003:Brucella abortus / Q000187:drug effects*; D002006:Brucellosis / Q000382:microbiology; D002460:Cell Line; D004339:Drug Compounding; D005839:Gentamicins / Q000008:administration & dosage / Q000494:pharmacology*; D019344:Lactic Acid; D051379:Mice; D008863:Microspheres; D009000:Monocytes / Q000187:drug effects / Q000382:microbiology*; D010316:Particle Size; D010587:Phagocytosis; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D016897:Respiratory Burst / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid