聚乙二醇修饰小分子药物的研究进展

Research Progress in PEG Prodrug

以高聚物作为载体,携带各种活性化合物组成药物释放系统,在现代医疗中发挥了巨大的作用。高分子偶联物不仅可以改变药物的药动学特征,还可以通过偶联特异性的物质使药物具有主动靶向性。目前研究最广泛的高分子载体是聚乙二醇。聚乙二醇通过与肽链、抗体、酶等活性化合物偶联,可以提高药物溶解度,延长循环半衰期,减少非特异性摄取,增加靶向性。已有很多聚乙二醇修饰的药物上市,也有很多尚处于临床研究阶段。大部分聚乙二醇化药物的临床研究表明,聚乙二醇修饰的药物确实可以提高药效、降低毒副作用。但关于聚乙二醇修饰小分子药物的设计依然需要进一步研究和完善。我们主要讨论聚乙二醇修饰小分子药物的设计和应用。

The field of drug delivery system utilizing polymeric carrier, which covalently conjugates molecule of interest, plays an important role in modern therapeutics. In this model, it was envisioned that not only could the pharmacokinetics of the drug attached to the polymeric carrier be modulated but also that active targeting could be achieved if a homing moiety was introduced to the same polymeric carrier. Recently, polyethylene glycol（PEG） is the most widely used as polymeric carrier. PEGylation of peptides, proteins, drugs and bioactives is known to enhance the aqueous solubility of hydrophobic drugs, prolong circulation time, minimize nonspecific uptake, and achieve specific tumor targetability. Numerous PEG-based therapeutics have been developed, and several have received market approval. A vast amount of clinical experience has been gained which has helped to design PEG prodrug conjugates with improved therapeutic efficacy and reduced systemic toxicity. However, more efforts in designing PEG-based prodrug conjugates are anticipated. In light of this, the paper highlights synthetic advances in PEG prodrug conjugation methodologies with varied bioactive components of clinical relevance. In addition, this paper discusses FDA-approved PEGylated delivery systems, their intended clinical applications.