Targeted Delivery Should Be Designed Around Competing Biological Sinks

Targeted drug delivery is usually framed as a problem of increasing affinity for a desired tissue or cell. That framing is incomplete because an administered carrier is simultaneously exposed to biological compartments that remove, retain, transform, redistribute, or consume it before and after target contact. These competing sinks include the mononuclear phagocyte system, liver and spleen, renal and pulmonary pathways, adsorbed proteins, nontarget cellular populations, and finite receptor pools