Dendrimer versus linear conjugate: Influence of polymeric architecture on the delivery and anticancer effect of paclitaxel
Dendrimer versus linear conjugate: Influence of polymeric architecture on the delivery and anticancer effect of paclitaxel
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DOI：
10.1021/bc060240p
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发表时间：
2006-11-15
影响因子：
4.7
通讯作者：
Minko, Tamara
中科院分区：
文献类型：
--
作者：
Khandare, Jayant J.;Jayant, Sreeja;Minko, Tamara
已经描述了与紫杉醇缀合的树枝状聚合物和线性双（聚（乙二醇））（PEG）聚合物的聚合物结构的相对差异。紫杉醇是一种难溶性抗癌药物，与PAMAM G4羟基封端的树枝状聚合物和双（PEG）聚合物共价结合，以提高药物的溶解度和细胞毒性。通过（NMR）-N-1、HPLC和MALDI/TOF表征两种缀合物。此外，通过分子模拟研究了树状大分子、双（PEG）、紫杉醇及其聚合物偶联物的分子构象。使用酯酶水解酶通过HPLC分析缀合物中酯键的水解。使用A2780人卵巢癌细胞评价树状聚合物、双（PEG）、紫杉醇和含有紫杉醇的聚合物缀合物的体外细胞毒性。与游离非缀合药物相比，PAMAM树枝状聚合物-琥珀酸-紫杉醇缀合物的细胞毒性增加了10倍。所获得的数据表明，纳米尺寸的树枝状聚合物缀合物可以作为抗癌药物载体，并取得了良好的成功。
The relative difference in polymeric architectures of dendrimer and linear bis( poly( ethylene glycol)) ( PEG) polymer in conjugation with paclitaxel has been described. Paclitaxel, a poorly soluble anticancer drug, was covalently conjugated with PAMAM G4 hydroxyl-terminated dendrimer and bis( PEG) polymer for the potential enhancement of drug solubility and cytotoxicity. Both conjugates were characterized by (NMR)-N-1, HPLC, and MALDI/TOF. In addition, molecular conformations of dendrimer, bis( PEG), paclitaxel, and its polymeric conjugates were studied by molecular modeling. Hydrolysis of the ester bond in the conjugate was analyzed by HPLC using esterase hydrolyzing enzyme. In vitro cytotoxicity of dendrimer, bis( PEG), paclitaxel, and polymeric conjugates containing paclitaxel was evaluated using A2780 human ovarian carcinoma cells. Cytotoxicity increased by 10-fold with PAMAM dendrimer-succinic acid-paclitaxel conjugate when compared with free nonconjugated drug. Data obtained indicate that the nanosized dendritic polymer conjugates can be used with good success as anticancer drug carriers.