Dragojevic Sonja, Ryu Jung Su, Raucher Drazen
Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street Jackson, MS 39216, USA.
Molecules. 2015 Dec 4;20(12):21750-69. doi: 10.3390/molecules201219804.
The majority of anticancer drugs have poor aqueous solubility, produce adverse effects in healthy tissue, and thus impose major limitations on both clinical efficacy and therapeutic safety of cancer chemotherapy. To help circumvent problems associated with solubility, most cancer drugs are now formulated with co-solubilizers. However, these agents often also introduce severe side effects, thereby restricting effective treatment and patient quality of life. A promising approach to addressing problems in anticancer drug solubility and selectivity is their conjugation with polymeric carriers to form polymer-based prodrugs. These polymer-based prodrugs are macromolecular carriers, designed to increase the aqueous solubility of antitumor drugs, can enhance bioavailability. Additionally, polymer-based prodrugs approach exploits unique features of tumor physiology to passively facilitate intratumoral accumulation, and so improve chemodrug pharmacokinetics and pharmacological properties. This review introduces basic concepts of polymer-based prodrugs, provides an overview of currently emerging synthetic, natural, and genetically engineered polymers that now deliver anticancer drugs in preclinical or clinical trials, and highlights their major anticipated applications in anticancer therapies.
大多数抗癌药物的水溶性较差，会对健康组织产生不良反应，因此对癌症化疗的临床疗效和治疗安全性都造成了重大限制。为了帮助解决与溶解度相关的问题，目前大多数抗癌药物都与助溶剂一起配制。然而，这些试剂往往也会带来严重的副作用，从而限制了有效治疗和患者的生活质量。解决抗癌药物溶解度和选择性问题的一种有前景的方法是将它们与聚合物载体缀合以形成基于聚合物的前药。这些基于聚合物的前药是大分子载体，旨在提高抗肿瘤药物的水溶性，可提高生物利用度。此外，基于聚合物的前药方法利用肿瘤生理学的独特特征来被动促进肿瘤内蓄积，从而改善化疗药物的药代动力学和药理学性质。本文综述介绍了基于聚合物的前药的基本概念，概述了目前正在进行临床前或临床试验的用于递送抗癌药物的新型合成聚合物、天然聚合物和基因工程聚合物，并强调了它们在抗癌治疗中的主要预期应用。
