Macromolecular versus small-molecule therapeutics: drug discovery, development and clinical considerations

Recent advances in biomedical science in general, and molecular biology in particular, have provided a greater understanding of pathogenesis at the molecular and (sub)cellular level. In turn, this has stimulated the development of macromolecular, mechanism-based therapeutic agents, ranging from recombinant proteins, to oligonucleotides, to genes/gene fragments. The factors essential for the successful development of this new class of therapeutic agents are not necessarily the same as those for the development of conventional small organic molecules. This review mentions several issues relating to the development of macromolecular drugs, and emphasizes the key issue of drug transport and delivery.