Control of pharmacokinetic profiles of drug-macromolecule conjugates

Macromolecular conjugation is a useful method for controlling the pharmacokinetic profiles of small drugs, proteins, oligonucleotides and genes. Site-specific drug delivery can be achieved by the use of an appropriate macromolecular carrier which should have an affinity for the target tissue or cells. The rationale of this approach is to alter the disposition characteristics of a free drug by conjugating it to a suitable macromolecular carrier. The rational design of drug-macromolecule conjugates requires a thorough understanding of the relationship between their chemical structures, physicochemical properties and pharmacokinetics at whole body, organ, cellular and subcellular levels. In this article, the current status and future perspectives of macromolecular conjugates of conventional low molecular weight drugs, protein drugs and gene medicines, such as antisense oligonucleotides and plasmid DNA, are reviewed.