Precious Cargo: The Role of Polymeric Nanoparticles in the Delivery of Covalent Drugs

Abstract

Covalent drugs can offer significant advantages over non-covalent drugs in terms of pharmacodynamics (i.e., target-binding properties). However, the development of covalent drugs is sometimes hampered by pharmacokinetic limitations (e.g., low bioavailability, rapid metabolism and toxicity due to off-target binding). Polymeric nanoparticles offer a potential solution to these limitations. Delivering covalent drugs via polymeric nanoparticles provides myriad benefits in terms of drug solubility, permeability, lifetime, selectivity, controlled release and the opportunity for synergistic administration alongside other drugs. In this short review, we examine each of these benefits in turn, illustrated through multiple case studies.

Keywords

• targeted covalent inhibitors
• reactive drugs
• electrophilic warheads
• drug delivery
• nanomedicine
• polymeric nanoparticles