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Poly(D,L-lactide-coglycolide) particles containing gentamicin: pharmacokinetics and pharmacodynamics in Brucella melitensis-infected mice
Authors: Lecaroz, M.C. (María Concepción)
Blanco-Prieto, M.J. (María José)
Campanero, M.A. (Miguel Angel)
Salman, H.H. (Hesham H.)
Gamazo, C. (Carlos)
Keywords: Brucellosis
Gentamicin
Mice
PLGA
Issue Date: 2007
Publisher: American Society for Microbiology
Publisher version: http://dx.doi.org/10.1128/AAC.00809-06
ISSN: 0066-4804
Citation: Lecaroz MC, Blanco-Prieto MJ, Campanero MA, Salman H, Gamazo C. Poly(D,L-lactide-coglycolide) particles containing gentamicin: Pharmacokinetics and pharmacodynamics in brucella melitensis-infected mice. Antimicrob Agents Chemother. 2007 Apr;51(4):1185-90.
Abstract
Drug delivery systems containing gentamicin were studied as a treatment against experimental brucellosis in mice. Micro- and nanoparticles prepared by using poly(D,L-lactide-coglycolide) (PLGA) 502H and microparticles made of PLGA 75:25H were successfully delivered to the liver and the spleen, the target organs for Brucella melitensis. Both polymers have the same molecular weight but have different lactic acid/glycolic acid ratios. Microparticles of PLGA 502H and 75:25H released their contents in a sustained manner, in contrast to PLGA 502H nanoparticles, which were degraded almost completely during the first week postadministration. The values of the pharmacokinetic parameters after administration of a single intravenous dose of 1.5 mg/kg of body weight of loaded gentamicin revealed higher areas under the curve (AUCs) for the liver and the spleen and increased mean retention times (MRTs) compared to those for the free drug, indicating the successful uptake by phagocytic cells in both organs and the controlled release of the antibiotic. Both gentamicin-loaded PLGA 502H and 75:25H microparticles presented similar pharmacokinetic parameter values for the liver, but those made of PLGA 75:25 H were more effective in targeting the antibiotic to the spleen (higher AUCs and MRTs). The administration of three doses of 1.5 mg/kg significantly reduced the load associated with the splenic B. melitensis infection. Thus, the formulation made with the 75:25H polymer was more effective than that made with 502H microspheres (1.45-log and 0.45-log reductions, respectively, at 3 weeks posttreatment). Therefore, both, pharmacokinetic and pharmacodynamic parameters showed the suitability of 75:25H microspheres to reduce the infection of experimentally infected mice with B. melitensis.
Permanent link: http://hdl.handle.net/10171/19114
Appears in Collections:DA - CUN - Farmacología clínica - Artículos de revista
DA - Farmacia - Tecnología Farmacéutica - Artículos de revista
DA - Medicina - Microbiología y Parasitología - Artículos de revista

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