Conformation of surface-decorating dextran chains affects the pharmacokinetics and biodistribution of doxorubicin-loaded nanoparticles
Conformation of surface-decorating dextran chains affects the pharmacokinetics and biodistribution of doxorubicin-loaded nanoparticles
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DOI：
10.1016/j.ejpb.2012.03.009
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发表时间：
2012-06-01
影响因子：
4.9
通讯作者：
Moussa, Fathi
中科院分区：
文献类型：
--
作者：
Alhareth, Khairallah;Vauthier, Christine;Moussa, Fathi
最近的报道表明，纳米颗粒表面性质的细微改变会引起与血清蛋白相互作用的剧烈变化。本研究旨在研究修饰聚氰基丙烯酸烷基酯（PACA）纳米颗粒表面的葡聚糖链构象对模型药物的药代动力学和生物分布的影响。将阿霉素与阴离子乳液聚合（AEP） （Dox-AEP）和氧化还原自由基乳液聚合（RREP） （Dox-RREP）制备的PACA纳米粒子结合。大鼠静脉注射纳米颗粒和游离药物（f-Dox），测定阿霉素的药代动力学和生物分布。药代动力学曲线表现为快速分布期和缓慢消除期。Dox-RREP的分布期药代动力学参数与f-Dox和Dox-AEP的分布期药代动力学参数有显著差异，而三种制剂的消除期药代动力学参数无显著差异。与其他制剂相比，用Dox- rrep处理的大鼠肝脏中的Dox浓度较低，但心脏、肺和肾脏中的Dox浓度较高。Dox-RREP表现出一种新型的潜行行为，其循环时间短，在血管化程度高的器官内分布迅速，绕过MPS。两种纳米颗粒配制的药物在药代动力学和生物分布上的差异归因于纳米颗粒表面的葡聚糖链构象的差异。(C) 2012 Elsevier B.V.版权所有
Recent reports showed that subtle modifications of nanoparticle surface properties induced dramatic changes of interactions with serum proteins. The present work was aimed to investigate the effect of the conformation of dextran chains decorating-the surface of poly(alkylcyanoacrylate) (PACA) nanoparticles on the pharmacokinetic and biodistribution of a model drug associated with the nanoparticles. Doxorubicin was associated with PACA nanoparticles prepared by anionic emulsion polymerization (AEP) (Dox-AEP) and redox radical emulsion polymerization (RREP) (Dox-RREP). Nanoparticles and the free drug (f-Dox) were injected intravenously to rats to determine the pharmacokinetic and biodistribution of doxorubicin. Curves of the pharmacokinetics showed a rapid phase of distribution followed by a slower elimination phase. Pharmacokinetic parameters of the distribution phase determined for the Dox-RREP were significantly different from those of f-Dox and Dox-AEP, while no difference was observed in the elimination phase of the three formulations. Rats treated with Dox-RREP showed lower Dox concentrations in liver but higher concentrations in heart, lungs, and kidneys compared to those treated with the other formulations. Dox-RREP exhibited a new type of stealth behavior characterized by a short circulation time and a rapid distribution in highly vascularized organs bypassing the MPS. The difference in pharmacokinetic and biodistribution observed between the drugs formulated with the two types of nanoparticles was attributed to the difference in the conformation of the dextran chains stranded on the nanoparticle surface. (C) 2012 Elsevier B.V. All rights reserved.