In vitro and in vivo evaluation of hydrophilic dendronized linear polymers
In vitro and in vivo evaluation of hydrophilic dendronized linear polymers
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DOI：
10.1021/bc0497665
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发表时间：
2005-05-01
影响因子：
4.7
通讯作者：
Szoka, FC
中科院分区：
文献类型：
--
作者：
Lee, CC;Yoshida, M;Szoka, FC
由聚（4-羟基苯乙烯）主链和第四代聚酯树枝状分子组成的刚性棒树枝状线性聚合物在体外和体内进行了评估，以确定它们作为药物递送载体的适用性。细胞毒性测定表明该聚合物在体外被细胞良好耐受。对非肿瘤和肿瘤小鼠中聚合物的生物分布研究表明，对于无规卷曲线性聚合物，肾清除率是聚合物尺寸的函数，对于 67 kDa 树枝状聚合物观察到显着的尿排泄。具有非常高分子量（M-n = 1740 kDa）的树枝化聚合物表现出在网状内皮系统器官中的高积累，但对于 Mn = 67 kDa 和 M. = 251 kDa 的较小聚合物则不那么显着。以每克肿瘤注射剂量百分比为基础的聚合物的肿瘤累积排序为251 kDa，类似于1740 kDa > 67 kDa。这些数据将有助于指导选择具有适合用作药物载体的药代动力学特性的高度可功能化的刚性棒树枝化聚合物。
Rigid-rod dendronized linear polymers consisting of a poly(4-hydroxystyrene) backbone and fourth-generation polyester dendrons were evaluated in vitro and in vivo to determine their suitability as drug delivery vectors. Cytotoxicity assays indicated that the polymers were well tolerated by cells in vitro. Biodistribution studies of the polymers in both nontumored and tumored mice revealed that as for random coil linear polymers, renal clearance was a function of polymer size, with significant urinary excretion observed for a 67 kDa dendronized polymer. High accumulation in organs of the reticuloendothelial system was exhibited by a dendronized polymer with a very high molecular weight (M-n = 1740 kDa), but was not as significant for smaller polymers with Mn = 67 kDa and M. = 251 kDa. The rank order for tumor accumulation of the polymers on a percent injected dose per gram tumor basis was 251 kDa similar to 1740 kDa > 67 kDa. These data will help guide the selection of highly fanctionalizable rigid-rod dendronized polymers with pharmacokinetic properties appropriate for use as drug carriers.