Targeted Prodrugs in Oral Drug Delivery

Milica Markovic, Shimon Ben-Shabat, Arik Dahan

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


The prodrug approach is no longer considered as a last option for improving drug-like features of compounds, but rather it is considered at the early stages of drug development. Molecular revolution led to innovations in the drug development process, and instead of depending on empirical fitting based on plasma levels, the novel ADME (absorption, distribution, metabolism, and elimination) research takes into account molecular and cellular parameters (e.g. membrane influx/efflux transporters, expression, and distribution of cellular proteins). This led to novel-targeted prodrug approach that uses carrier-mediated transport to increase intestinal permeability, as well as specific prodrug activating enzymes. Targeting enzymes, such as valacyclovirase, phospholipase A 2 (PL A 2), as well as peptide transporter 1 (PEPT1), monocarboxylate transporter (MCT1), peptide transporter 1 (PEPT1), and bile acid transporter (ASBT), are demonstrated as effective examples of such approach. In addition, in silico methods, such as molecular dynamics (MD) or density functional theory (DFT), are presented as a useful tool for optimizing drug design for successful binding to target sites. In conclusion, the prodrug approach is no longer viewed as merely a chemical derivatization of the drug, but rather as a new way of exploiting physiological targets to accomplish optimal effect, overcoming various oral drug-delivery problems, as well as target limitations. In the coming years, this field is expected to grow, as greater knowledge of intestinal transporters and activating enzymes becomes available.

Original languageEnglish
Title of host publicationTargeted Drug Delivery
Number of pages24
ISBN (Electronic)9783527827855
ISBN (Print)9783527347810
StatePublished - 1 Jan 2022


  • Biopharmaceutics
  • Drug targeting
  • Oral drug delivery
  • Prodrugs
  • Transporters enzymes

ASJC Scopus subject areas

  • Chemistry (all)


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