Targeted prodrugs in oral drug delivery: the modern molecular biopharmaceutical approach.
BACKGROUND
The molecular revolution greatly impacted the field of drug design and delivery in general, and the utilization of the prodrug approach in particular. The increasing understanding of membrane transporters has promoted a novel 'targeted-prodrug' approach utilizing carrier-mediated transport to increase intestinal permeability, as well as specific enzymes to promote activation to the parent drug.


METHODS
This article provides the reader with a concise overview of this modern approach to prodrug design. Targeting the oligopeptide transporter PEPT1 for absorption and the serine hydrolase valacyclovirase for activation will be presented as examples for the successful utilization of this approach. Additionally, the use of computational approaches, such as DFT and ab initio molecular orbital methods, in modern prodrugs design will be discussed.


CONCLUSIONS
Overall, in the coming years, more and more information will undoubtedly become available regarding intestinal transporters and potential enzymes that may be exploited for the targeted modern prodrug approach. Hence, the concept of prodrug design can no longer be viewed as merely a chemical modification to solve problems associated with parent compounds. Rather, it opens promising opportunities for precise and efficient drug delivery, as well as enhancement of treatment options and therapeutic efficacy.
Ben-Gurion University of the Negev, School of Pharmacy, Faculty of Health Sciences, Department of Clinical Pharmacology, P.O. Box 653, Beer-Sheva 84105, Israel. arikd@bgu.ac.il
Arik
A
Dahan
Mustafa
M
Khamis
Riad
R
Agbaria
Rafik
R
Karaman
D000284:Administration, Oral; D000818:Animals; D001688:Biological Products; D001692:Biological Transport; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry
D001688:Biological Products; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; D011355:Prodrugs