JAC Advance Access published online on April 21, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh227
© 2004 by The British Society for Antimicrobial Chemotherapy
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1 Department of Microbiology, University of Navarra,
31008 Pamplona, Spain;
* To whom correspondence should be addressed. E-mail: cgamazo{at}unav.es.
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) 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 µg
of free or microencapsulated gentamicin and the efficacy of the
treatments was measured after 24 h. Results: The particle sizes were below 8 µm 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 log10) in comparison with untreated
infected cells. Addition of 2% poloxamer 188 to the microsphere
dispersion medium further reduced the infection (3.5 log10).
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 ( 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.
Revised March 8, 2004
Accepted March 8, 2004
Original article
Gentamicin-loaded microspheres for reducing the
intracellular
Brucella abortus load in infected monocytes
2 Institute
of Pharmaceutical Sciences, ETH, 8057 Zürich, Switzerland
3 Department of Pharmacy and Pharmaceutical
Technology, University of Navarra,
31008 Pamplona, Spain;
Abstract 
1
log10 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.
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