Absorption of Polyethylene Glycol (PEG) Polymers: The Effect of PEG Size on Permeability
Absorption of Polyethylene Glycol (PEG) Polymers: The Effect of PEG Size on Permeability
复制标题
DOI：
10.1002/jps.21635
复制
发表时间：
2009-08-01
影响因子：
3.8
通讯作者：
Fishburn, C. Simone
中科院分区：
文献类型：
--
作者：
Gursahani, Hema;Riggs-Sauthier, Jennifer;Fishburn, C. Simone
聚乙二醇（PEG）聚合物是在溶液中高度水合的大的两亲分子。为了探索不同大小的PEG聚合物在体内穿过上皮膜的渗透性，我们检查了来自肺的大小为0.55-20 kDa的荧光标记的PEG缀合物的吸收，因为该系统提供了限制分子快速扩散远离递送部位的储库，并且能够检查更长时间的渗透性。在大鼠体内给药后，PEG聚合物以单指数衰减曲线描述的一级动力学进行吸收。PEG的大小产生了显着的影响，从肺的摄取率，半衰期范围为2.4至13小时，虽然以上的大小为5 kDa，没有进一步的变化率观察。PEG大小同样影响肺泡巨噬细胞和肺组织中的保留;而较小的PEG大小（5 kDa）在肺细胞和组织中保留长达7天。这些数据表明，PEG聚合物可以通过上皮细胞膜吸收，并且PEG大小在控制吸收速率和机制方面起主导作用。(C)2009 Wiley-Liss，Inc.和American Pharmacologist Association J Pharm Sci 98：2847-2856，2009
Polyethylene glycol (PEG) polymers are large amphiphilic molecules that are highly hydrated in solution. To explore the permeability properties of different sized PEG polymers across epithelial membranes in vivo, we examined the absorption of fluorescently labeled PEG conjugates sized 0.55-20 kDa from the lung, since this system provides a reservoir that limits rapid diffusion of molecules away from the site of delivery and enables permeability over longer times to be examined. Following intratracheal delivery in rats, the PEG polymers underwent absorption with first-order kinetics described by single exponential decay curves. PEG size produced a marked influence on the rate of uptake from the lung, with half-lives ranging from 2.4 to 13 h, although above a size of 5 kDa, no further change in rate was observed. PEG size likewise affected retention in alveolar macrophages and in lung tissue; whereas smaller PEG sizes (5 kDa) remained in lung cells and tissue for up to 7 days. These data demonstrate that PEG polymers can be absorbed across epithelial membranes and that PEG size plays a dominant role in controlling the rate and mechanism of absorption. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2847-2856, 2009