Li Chun, Wallace Sidney
Department of Experimental Diagnostic Imaging, Unit 59, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Adv Drug Deliv Rev. 2008 May 22;60(8):886-98. doi: 10.1016/j.addr.2007.11.009. Epub 2008 Feb 8.
Targeted drug delivery aims to increase the therapeutic index by making more drug molecules available at the diseased sites while reducing systemic drug exposure. In this update, we provide an overview of polymer-drug conjugates that have advanced into clinical trials. These systems use synthetic water-soluble polymers as the drug carriers. The preclinical pharmacology and recent data in clinical trials with poly(l-glutamic acid)-paclitaxel (PG-TXL) are discussed. This is followed by a summary of a variety of polymeric conjugates with chemotherapeutic agents. Results from early clinical trials of these polymer-drug conjugates have demonstrated several advantages over the corresponding parent drugs, including fewer side effects, enhanced therapeutic efficacy, ease of drug administration, and improved patient compliance. Collectively, these data warrant further clinical development of polymer-drug conjugates as a new class of anticancer agents.
靶向给药旨在通过使更多药物分子在患病部位发挥作用,同时减少全身药物暴露来提高治疗指数。在本次更新中,我们概述了已进入临床试验阶段的聚合物-药物偶联物。这些系统使用合成水溶性聚合物作为药物载体。讨论了聚(L-谷氨酸)-紫杉醇(PG-TXL)的临床前药理学及近期临床试验数据。随后总结了多种与化疗药物结合的聚合物偶联物。这些聚合物-药物偶联物早期临床试验结果显示,相较于相应的母体药物具有多项优势,包括副作用更少、治疗效果增强、给药方便以及患者依从性提高。总体而言,这些数据表明聚合物-药物偶联物作为一类新型抗癌药物值得进一步开展临床研究。