Gentamicin-loaded microspheres for reducing the intracellular Brucella abortus load in infected monocytes.
J Antimicrob Chemother
; 53(6): 981-8, 2004 Jun.
Article
em En
| MEDLINE
| ID: mdl-15102748
ABSTRACT
OBJECTIVES:
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) 5050 (PLGA 5050 and PLGA 5050H) 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 5050H) or a multiphasic (PLGA 5050) pattern over 50 days. Treatment with gentamicin microencapsulated into the end-group uncapped PLGA 5050H 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 5050 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 5050 and PLGA 5050H microspheres had no bactericidal activity.CONCLUSIONS:
The results indicate that PLGA 5050-microencapsulated gentamicin sulphate may be suitable for efficient drug targeting and delivery to reduce intracellular Brucella infections.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Brucella abortus
/
Gentamicinas
/
Monócitos
/
Antibacterianos
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article