Promotion of optimized protein therapy by bioconjugation as a polymeric DDS
Promotion of optimized protein therapy by bioconjugation as a polymeric DDS
复制标题
DOI：
10.2174/187152006776930864
复制
发表时间：
2006-05-01
影响因子：
2.8
通讯作者：
Nakagawa, Shinsaku
中科院分区：
文献类型：
--
作者：
Abe, Yasuhiro;Shibata, Hiroko;Nakagawa, Shinsaku
近年来，重组产生的生物活性蛋白如细胞因子的临床应用引起了人们的关注。然而，由于这些重组蛋白在体内相当不稳定，它们作为治疗剂的临床应用需要以高剂量频繁给药。这种疗法破坏了体内平衡，并导致严重的副作用。为了克服这些问题，已经将生物活性蛋白质与水溶性合成（WSS）聚合物载体缀合。用WSS聚合物载体对蛋白质进行化学修饰（生物缀合）调节组织分布，导致其期望的治疗效果的选择性增加和不期望的副作用的减少。在多种药物递送系统（DDS）技术中，生物缀合已被认为是提高蛋白质治疗效力的最有效方法之一。然而，为了进一步增强缀合的生物活性蛋白的治疗效力和安全性，需要更精确地调节每种蛋白的体内行为以选择性地表达其治疗效果。因此，需要替代的WSS聚合物改性剂，其中可以添加新的功能，如靶向和药物的控释，以进一步开发生物缀合药物。最近，我们合成了一种新型的高分子药物载体，聚（乙烯基吡咯烷酮-co-二甲基马来酸酐）[PVD]，这是一个强大的候选药物载体的癌症治疗。本文就高分子药物载体的设计及其在蛋白质治疗中的应用作一综述，
In recent years, clinical applications of recombinantly produced bioactive proteins such as cytokines have attracted attention. However, since these recombinant proteins are rather unstable in vivo, their clinical use as therapeutic agents requires frequent administration at a high dosage. This regimen disrupts homeostasis and results in severe side effects. To overcome these problems, bioactive proteins have been conjugated with water-soluble synthetic (WSS) polymeric carriers. Chemical modification of a protein with a WSS polymeric carrier (bioconjugation) regulates tissue distribution, resulting in a selective increase in its desirable therapeutic effects and a decrease in undesirable side effects. Among several drug deliver), system (DDS) technologies, bioconjugation has been recognized as one of the most efficient methods for improving therapeutic potency of proteins. However, for further enhancement of the therapeutic potency and safety of conjugated bioactive proteins, more precise regulation of the in vivo behavior of each protein is necessary for selective expression of its therapeutic effect. Therefore, alternative WSS polymeric modifiers in which new functions such as targeting and controlled release of drugs can be added are required for further development of bioconjugated drugs. Recently, we have synthesized a novel polymeric drug carrier, poly(vinylpyrrolidone-co-dimethyl maleic anhydride) [PVD], which was a powerful candidate drug carrier for cancer therapy. In this review, we introduce useful information that enabled us to design polymeric drug carriers and their application for protein therapy,