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Prodrug Design to Enhance Bioavailability and Systemic Delivery

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Systemic Delivery Technologies in Anti-Aging Medicine: Methods and Applications

Part of the book series: Healthy Ageing and Longevity ((HAL,volume 13))

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Abstract

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.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil

    Bruna Machado Araújo Sanches & Elizabeth Igne Ferreira

Authors
  1. Bruna Machado Araújo Sanches
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  2. Elizabeth Igne Ferreira
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Correspondence to Elizabeth Igne Ferreira .

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Editors and Affiliations

  1. School of Life and Health Sciences, The Chinese University of Hong Kong (Shenzhen), Shenzhen, China

    Wing-Fu Lai

Glossary

ADME

An acronym referring to absorption, distribution, metabolism and excretion of a compound upon administration to a biological body.

Bioactive compound

A compound that presents biological activity but is not a drug yet.

Biotransformation

The conversion of a chemical entity from one form to another form by means of a biological system.

Gene-directed enzyme prodrug therapy

A two-step process in which a gene encoding an enzyme is first delivered to a target cell, followed by the administration of a nontoxic prodrug that can be converted to a cytotoxin under the action of the enzyme.

Hit

A molecule which has a known structural identity and at the same time shows reproducible activity above a defined threshold in a biological assay.

Lead

A compound (or compound series) which on one hand display desirable biological activity in a relevant cell-based assay and on the other hand demonstrates proper activity, selectivity, and tractable structure-activity relationship. It is a candidate for further structure-activity optimization.

Medicinal chemistry

A discipline in chemistry which concerns with the invention, discovery, identification, design, and preparation of bioactive compounds. In addition, the metabolism and the mode of action of those compounds at the molecular level, along with the structure-activity relationships, will be studied in medicinal chemistry.

Molecular modification

Processes that give rise to changes in some characteristics of a compound/drug towards optimization.

Receptors

Molecules or polymeric structures present on the cell surface or in the cell. They can recognize and bind other agents which serve as molecular messengers (e.g. neurotransmitters, hormones, and drug molecules) in a body.

Valley of death

The occurrence of problems (e.g. o lack of solubility and high toxicity) that avoid the innovative molecule to pass through the development phase and prevent it from finally reaching the clinical phase as a drug candidate.

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Sanches, B.M.A., Ferreira, E.I. (2020). Prodrug Design to Enhance Bioavailability and Systemic Delivery. In: Lai, WF. (eds) Systemic Delivery Technologies in Anti-Aging Medicine: Methods and Applications. Healthy Ageing and Longevity, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-030-54490-4_5

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