Prodrug Design to Enhance Bioavailability and Systemic Delivery

In the preceding two chapters in Section I, different strategies used to characterize the properties and performance of a drug, which can be either a free drug or a drug that has been loaded into a carrier, have been discussed. From Section II onward, selected strategies to enhance systemic drug delivery will be presented. As the first chapter in this section, we will introduce the concept of prodrug design. In fact, prodrugs have been very important to solve many problems with leads and drugs. The optimization of leads can overcome the “valley of death,” allowing the drug candidate to reach clinical phases. On the other hand, drugs can be optimized even though they have been launched in the therapeutics, improving their usage and patient adherence. Pharmaceutical, pharmacokinetics, and, indirectly, pharmacodynamic problems of leads and drugs can be managed by prodrug design. In this chapter, we will present some classical and recent examples related to bioavailability, prolonged action, reduction of toxicity and, mainly, selectivity of action, and will also introduce some of the drugs approved by FDA to illustrate the use of prodrug design in reality.