Polymer-drug conjugates: Origins, progress to date, and future directions

Polymers have been utilized to deliver drugs to the targeted site in a controlled manner and for achieving high therapeutic efficacy. Polymer-drug conjugates having variable ligands have been proved to be biodegradable, stimuli-sensitive, and targeted systems and can be effectively used for the delivery of drugs to the target site. Numerous polymer-drug conjugates having linkers degraded by acidity or intracellular enzymes or sensitive to overexpressed groups of diseased organs/tissues have been synthesized during the last decade to develop targeted delivery systems. Polymer-drug conjugates are a novel class of nanocarriers for drug delivery, which can protect drugs from premature degradation, prevent drugs from premature interaction with the biological environment, and enhance the absorption of the drugs into tissues. Polymer-drug conjugates are often considered as new chemical entities (NCEs) owing to a pharmacokinetic profile distinct from that of the parent drug. Synthetic polymers may be conjugated covalently to a variety of natural or synthetic biomolecules for many diverse uses. Polymer conjugation is an efficient approach for improving the therapeutic properties of bioactives. Since the first synthetic polymer-drug conjugate entered clinical trials in 1994, this technology has undergone notable development for the introduction and study of novel polymers and for progress in the biological rationale for designing conjugates. Not surprisingly, new polymers, in addition to the best-known polyethylene glycol, poly(N-(2-hydroxypropyl) methacrylamide), are continuously conjugated with drugs to achieve biodegradable, stimuli-sensitive, and targeted systems in an attempt to prolong blood circulation times and enhance drug concentrations at the intended site of action. This chapter highlights the approaches for designing polymer-drug conjugates, future prospects of polymer-drug conjugates, the gap between current studies and clinical application for polymer-drug conjugates, approaches for enhancing the transportation of polymer-drug conjugates, clinical status of polymer-drug conjugates, and patent status of polymer-drug conjugates.