Recent advances in macromolecular prodrugs

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. (C) 2017 Elsevier Ltd. All rights reserved.