Pasut Gianfranco, Sergi Mauro, Veronese Francesco M
Department of Pharmaceutical Sciences, University of Padua, via Marzolo 5, 35100 Padua, Italy.
Adv Drug Deliv Rev. 2008 Jan 3;60(1):69-78. doi: 10.1016/j.addr.2007.04.018. Epub 2007 Aug 11.
PEGylation (i.e. the covalent link of PEG strands) is a well known technique used to improve pharmaceutical properties of bioactive proteins and peptides. Even in cancer therapy some proteins, in particular enzymes, can find many applications, because of their antiproliferative action or ability to reduce side effects of chemotherapies, but to do so they need to be properly formulated. Unfortunately, formulation alone can not fulfil all the requirements to yield a safe and successful protein preparation for therapeutic applications. In particular, for many proteins fast clearance from the body and potential immunogenicity are severe limitations, which can not be easily overcome without taking into consideration a purposely designed drug delivery system. Among the approaches in the field of drug delivery, PEGylation has so far been the best choice for protein delivery. Here, we describe some examples of PEGylated enzymes useful in antitumoral therapies and the most recent advances in this field.
聚乙二醇化(即聚乙二醇链的共价连接)是一种众所周知的用于改善生物活性蛋白质和肽类药物性质的技术。即使在癌症治疗中,一些蛋白质,特别是酶,因其抗增殖作用或降低化疗副作用的能力,也能有许多应用,但要做到这一点,它们需要经过适当的制剂配方。不幸的是,仅靠制剂配方并不能满足生产出用于治疗应用的安全且成功的蛋白质制剂的所有要求。特别是,对于许多蛋白质来说,从体内快速清除以及潜在的免疫原性是严重的限制因素,如果不考虑专门设计的药物递送系统,这些问题很难轻易克服。在药物递送领域的诸多方法中,聚乙二醇化迄今为止一直是蛋白质递送的最佳选择。在此,我们描述一些用于抗肿瘤治疗的聚乙二醇化酶的实例以及该领域的最新进展。