Prodrug Approaches to Drug Delivery

This chapter focuses on the various prodrug approaches that have been used to overcome many of the pharmaceutical and pharmacokinetic barriers that hinder the optimal delivery of the active drug. The most important requirement in prodrug design is naturally the adequate reconversion of the prodrug to the active drug in vivo at the intended compartment. This prodrug‐drug conversion may take place before absorption, in the GI system, during absorption such as in the GI wall or skin, after absorption, or at the specific site of drug action. A number of enzymes can also be delivered to targeted tissues through antibodies or gene delivery approaches for the activation of subsequently administered prodrugs. Although they are of limited use in small‐molecule pro‐drugs, Schiff bases have been used to conjugate amine‐containing drugs to polymers with carbonyl groups as macromolecular prodrugs for slow release and targeting.