Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, D-14195 Berlin, Germany.
J Control Release. 2011 May 10;151(3):295-301. doi: 10.1016/j.jconrel.2011.01.017. Epub 2011 Jan 21.
In an attempt to explore the potential of dendritic systems for the development of effective anticancer drug delivery systems, we explored a simple modular approach of preparing polyglycerol doxorubicin prodrugs, with flexibility for drug loading using an acid-sensitive hydrazone linker and further post-modification with poly(ethylene glycol) shell. The resulting drug polymer conjugates showed optimal properties for in vitro and in vivo applications because of their high water solubility, an appropriate size for passive tumor targeting, a high stability at physiological conditions, pronounced acid-sensitive properties, cellular internalization, and a favorable toxicity profile. Doxorubicin polyglycerol conjugates with a high drug loading ratio showed clearly improved antitumor efficacy over doxorubicin in an ovarian xenograft tumor model (A2780) inducing transient complete remissions thus demonstrating the potential of developing efficient multifunctional dendritic drug delivery using our modular approach.
为了探索树突状系统在开发有效抗癌药物传递系统方面的潜力，我们探索了一种简单的模块化方法来制备聚甘油阿霉素前药，该方法具有使用酸敏感腙键连接子进行药物负载的灵活性，并进一步用聚（乙二醇）壳进行后修饰。由于其高水溶性、适用于被动肿瘤靶向的合适尺寸、在生理条件下的高稳定性、明显的酸敏感性、细胞内化以及良好的毒性特征，所得药物聚合物缀合物表现出了非常适合于体外和体内应用的特性。与阿霉素相比，具有高载药率的聚甘油阿霉素缀合物在卵巢异种移植肿瘤模型（A2780）中显示出明显改善的抗肿瘤疗效，诱导短暂的完全缓解，从而证明了使用我们的模块化方法开发高效多功能树突状药物传递的潜力。
