Ryan Sinéad M, Mantovani Giuseppe, Wang Xuexuan, Haddleton David M, Brayden David J
University College Dublin, School of Agriculture, Food Science and Veterinary Medicine, Veterinary Sciences Building, Room 214, Belfield, Dublin 4, Ireland.
Expert Opin Drug Deliv. 2008 Apr;5(4):371-83. doi: 10.1517/17425247.5.4.371.
Although various injected peptide and protein therapeutics have been developed successfully over the past 25 years, several pharmacokinetic and immunological challenges are still encountered that can limit the efficacy of both novel and established biotech molecules.
PEGylation is a popular technique to address such properties. PEGylated drugs exhibit prolonged half-life, higher stability, water solubility, lower immunogenicity and antigenicity, as well as potential for specific cell targeting. Although PEGylated drug conjugates have been on the market for many years, the technology has steadily developed in respect of site-specific chemistry, chain length, molecular weights and purity of conjugate. These developments have occurred in parallel to improvements in physicochemical methods of characterization.
This review will discuss recent achievements in PEGylation processes with an emphasis on novel PEG-drugs constructs, the unrealized potential of PEGylation for non-injected routes of delivery, and also on PEGylated versions of polymeric nanoparticles, including dendrimers and liposomes.
尽管在过去25年中已成功开发出多种注射用肽和蛋白质疗法,但仍然面临一些药代动力学和免疫学方面的挑战,这些挑战可能会限制新型和已上市生物技术分子的疗效。
聚乙二醇化是解决此类特性的常用技术。聚乙二醇化药物具有延长的半衰期、更高的稳定性、水溶性、更低的免疫原性和抗原性,以及特异性细胞靶向的潜力。尽管聚乙二醇化药物缀合物已上市多年,但该技术在位点特异性化学、链长、分子量和缀合物纯度方面一直在稳步发展。这些发展与表征的物理化学方法的改进同时出现。
本综述将讨论聚乙二醇化过程中的最新成果,重点是新型聚乙二醇-药物构建体、聚乙二醇化在非注射给药途径中未实现的潜力,以及聚合物纳米颗粒(包括树枝状大分子和脂质体)的聚乙二醇化版本。