Poly(D,L-lactide-coglycolide) particles containing gentamicin:: Pharmacokinetics and pharmacodynamics in Brucella melitensis-infected mice
Poly(D,L-lactide-coglycolide) particles containing gentamicin:: Pharmacokinetics and pharmacodynamics in Brucella melitensis-infected mice
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DOI：
10.1128/aac.00809-06
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发表时间：
2007-04-01
影响因子：
4.9
通讯作者：
Gamazo, C.
中科院分区：
文献类型：
--
作者：
Lecaroz, M. C.;Blanco-Prieto, M. J.;Gamazo, C.
研究了含有庆大霉素的药物递送系统作为对小鼠实验性布鲁氏菌病的治疗。通过使用聚（D，L-丙交酯-共乙交酯）（PLGA）502 H和PLGA 75：25 H制成的微粒制备的微米和纳米颗粒被成功地递送到肝脏和脾脏，布鲁氏菌的靶器官。两种聚合物具有相同的分子量，但具有不同的乳酸/乙醇酸比例。PLGA 502 H和75：25 H的微粒以持续的方式释放其内容物，与PLGA 502 H纳米颗粒相反，PLGA 502 H纳米颗粒在给药后第一周几乎完全降解。单次静脉注射1.5 mg/kg体重的负载庆大霉素后的药代动力学参数值显示，与游离药物相比，肝脏和脾脏的曲线下面积（AUC）更高，平均保留时间（MRT）增加，表明两种器官中的吞噬细胞成功摄取抗生素，并控制释放。载庆大霉素的PLGA 502 H和75：25 H微粒对肝脏的药代动力学参数值相似，但由PLGA 75：25 H制成的微粒在将抗生素靶向脾脏方面更有效（AUC和MRT更高）。给予3个剂量的1.5 mg/kg显著降低了与脾脏B相关的负荷。羊种感染因此，用75：25 H聚合物制成的制剂比用502 H微球制成的制剂更有效（在治疗后3周分别减少1.45-log和0.45-log）。因此，药代动力学和药效学参数均表明75：25 H微球适用于减少实验感染小鼠的B感染。melitensis。
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.