Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
J Control Release. 2022 Aug;348:881-892. doi: 10.1016/j.jconrel.2022.05.060. Epub 2022 Jun 29.
Conjugation of poly(ethylene glycol) (PEG) to biologics is a successful strategy to favorably impact the pharmacokinetics and efficacy of the resulting bioconjugate. We compare bioconjugates synthesized by strain-promoted azide-alkyne cycloaddition (SPAAC) using PEG and linear polyglycerol (LPG) of about 20 kDa or 40 kDa, respectively, with an azido functionalized human Interferon-α2a (IFN-α2a) mutant. Site-specific PEGylation and LPGylation resulted in IFN-α2a bioconjugates with improved in vitro potency compared to commercial Pegasys. LPGylated bioconjugates had faster disposition kinetics despite comparable hydrodynamic radii to their PEGylated analogues. Overall exposure of the PEGylated IFN-α2a with a 40 kDa polymer exceeded Pegasys, which, in return, was similar to the 40 kDa LPGylated conjugates. The study points to an expanded polymer design space through which the selected polymer class may result in a different distribution of the studied bioconjugates.
聚乙二醇（PEG）与生物制剂的缀合是一种成功的策略，可以显著影响所得生物缀合物的药代动力学和疗效。我们比较了使用 PEG 和分别约 20 kDa 或 40 kDa 的线性聚甘油（LPG）通过应变促进的叠氮化物-炔烃环加成（SPAAC）合成的生物缀合物，与一个叠氮基功能化的人干扰素-α2a（IFN-α2a）突变体。与商业化的 Pegasys 相比，具有特定结合位点的 PEG 化和 LPG 化使 IFN-α2a 生物缀合物的体外效力得到改善。尽管 LPG 化生物缀合物的流体力学半径与其 PEG 类似物相当，但它们具有更快的处置动力学。具有 40 kDa 聚合物的 PEG 化 IFN-α2a 的总暴露量超过了 Pegasys，而 Pegasys 则与 40 kDa LPG 化缀合物相似。该研究指出了一个扩展的聚合物设计空间，通过该空间，所选的聚合物类别可能导致所研究的生物缀合物的不同分布。
