Macromolecular prodrugs (MP) are high molar mass conjugates, typically carrying several copies of a drug or a drug combination, designed to optimize delivery of the drug, that is — its pharmacokinetics. From its advent several decades ago, design of MP has undergone significant development and established solid guidelines for engineering successful MP in terms of the choice of the polymer carrier, its molar mass, and the choice of the linkage between the drug and the polymer. This review provides a brief account of the state-of-the-art in the development of MP and details the advantages of these tools of drug delivery. We also identify the challenges that need to be further addressed and offer a view on what is currently being done towards these goals. Specifically, we focus on i) the design of high molar mass, main-chain degradable polymers as drug carriers; ii) drug delivery using endogenous macromolecules such as albumin; iii) the choice of biodegradable linkages for drug delivery, and iv) the emerging interest in delivery of short-lived gasotransmitters. With this analysis and presentation, we aim to spur broader interest into MP to facilitate academic and translational development of MP.

大分子前药（MP）是高摩尔质量的结合物，通常带有几种拷贝的药物或药物组合，旨在优化药物的输送，即其药代动力学。从几十年前问世以来，MP的设计已经历了重大发展，并就聚合物载体的选择，其摩尔质量以及药物与聚合物之间的连接关系的选择，为工程成功的MP制定了坚实的指导方针。这篇综述简要介绍了MP的发展中的最新技术，并详细介绍了这些药物输送工具的优势。我们还确定了需要进一步解决的挑战，并对目前为实现这些目标正在采取的行动提供了看法。具体来说，我们专注于i）高摩尔质量的设计，主链可降解聚合物作为药物载体；ii）使用内源性大分子如白蛋白进行药物递送；iii）选择用于药物输送的可生物降解的连接，以及iv）对输送短寿命的气体递质的新兴兴趣。通过此分析和演示，我们旨在激发对MP的广泛兴趣，以促进MP的学术和翻译发展。