Dendrimer Versus Linear Conjugate: Influence of Polymeric Architecture on the Delivery and Anticancer Effect of Paclitaxel

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• 作者：Jayant J. Khandare ; Sreeja Jayant ; Ajay Singh ; Pooja Chandna ; Yang Wang ; Nicholi Vorsa ; Tamara Minko
• 刊名：Bioconjugate Chemistry
• 出版年：2006
• 出版时间：November 2006
• 年：2006
• 卷：17
• 期：6
• 页码：1464 - 1472
• 全文大小：341K
• 年卷期：v.17,no.6(November 2006)
• ISSN：1520-4812

文摘

The relative difference in polymeric architectures of dendrimer and linear bis(poly(ethylene glycol)) (PEG) polymerin conjugation with paclitaxel has been described. Paclitaxel, a poorly soluble anticancer drug, was covalentlyconjugated with PAMAM G4 hydroxyl-terminated dendrimer and bis(PEG) polymer for the potential enhancementof drug solubility and cytotoxicity. Both conjugates were characterized by ¹NMR, HPLC, and MALDI/TOF. Inaddition, molecular conformations of dendrimer, bis(PEG), paclitaxel, and its polymeric conjugates were studiedby molecular modeling. Hydrolysis of the ester bond in the conjugate was analyzed by HPLC using esterasehydrolyzing enzyme. In vitro cytotoxicity of dendrimer, bis(PEG), paclitaxel, and polymeric conjugates containingpaclitaxel was evaluated using A2780 human ovarian carcinoma cells. Cytotoxicity increased by 10-fold withPAMAM dendrimer-succinic acid-paclitaxel conjugate when compared with free nonconjugated drug. Dataobtained indicate that the nanosized dendritic polymer conjugates can be used with good success as anticancerdrug carriers.