Haag Rainer, Kratz Felix
Organic and Macromolecular Chemistry, Department of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
Angew Chem Int Ed Engl. 2006 Feb 13;45(8):1198-215. doi: 10.1002/anie.200502113.
Polymer therapeutics encompass polymer-protein conjugates, drug-polymer conjugates, and supramolecular drug-delivery systems. Numerous polymer-protein conjugates with improved stability and pharmacokinetic properties have been developed, for example, by anchoring enzymes or biologically relevant proteins to polyethylene glycol components (PEGylation). Several polymer-protein conjugates have received market approval, for example the PEGylated form of adenosine deaminase. Coupling low-molecular-weight anticancer drugs to high-molecular-weight polymers through a cleavable linker is an effective method for improving the therapeutic index of clinically established agents, and the first candidates have been evaluated in clinical trials, including, N-(2-hydroxypropyl)methacrylamide conjugates of doxorubicin, camptothecin, paclitaxel, and platinum(II) complexes. Another class of polymer therapeutics are drug-delivery systems based on well-defined multivalent and dendritic polymers. These include polyanionic polymers for the inhibition of virus attachment, polycationic complexes with DNA or RNA (polyplexes), and dendritic core-shell architectures for the encapsulation of drugs. In this Review an overview of polymer therapeutics is presented with a focus on concepts and examples that characterize the salient features of the drug-delivery systems.
聚合物疗法包括聚合物-蛋白质缀合物、药物-聚合物缀合物和超分子药物递送系统。例如，通过将酶或生物相关蛋白锚定到聚乙二醇组分上（聚乙二醇化），已经开发出了许多具有改善稳定性和药代动力学性质的聚合物-蛋白质缀合物。几种聚合物-蛋白质缀合物已获得市场批准，例如腺苷脱氨酶的聚乙二醇化形式。通过可裂解连接子将低分子量抗癌药物与高分子量聚合物偶联是提高临床已确立药物治疗指数的有效方法，首批候选药物已在临床试验中进行了评估，包括阿霉素、喜树碱、紫杉醇和铂（II）配合物的N-（2-羟丙基）甲基丙烯酰胺缀合物。另一类聚合物疗法是基于明确的多价和树枝状聚合物的药物递送系统。这些包括用于抑制病毒附着的聚阴离子聚合物、与DNA或RNA的聚阳离子复合物（多聚体）以及用于封装药物的树枝状核壳结构。在本综述中，对聚合物疗法进行了概述，重点关注表征药物递送系统显著特征的概念和实例。
