Co-opting biology to deliver drugs.

The goal of drug delivery is to improve the safety and therapeutic efficacy of drugs. This review focuses on delivery platforms that are either derived from endogenous pathways, long-circulating biomolecules and cells or that piggyback onto long-circulating biomolecules and cells. The first class of such platforms is protein-based delivery systems--albumin, transferrin, and fusion to the Fc domain of antibodies--that have a long-circulation half-life and are designed to transport different molecules. The second class is lipid-based delivery systems-lipoproteins and exosomes-that are naturally occurring circulating lipid particles. The third class is cell-based delivery systems--erythrocytes, macrophages, and platelets--that have evolved, for reasons central to their function, to exhibit a long life-time in the body. The last class is small molecule-based delivery systems that include folic acid. This article reviews the biology of these systems, their application in drug delivery, and the promises and limitations of these endogenous systems for drug delivery.