title: Targeted prodrug design to optimize drug delivery.
abstract: Classical prodrug design often represents a nonspecific chemical approach to mask undesirable drug properties such as limited bioavailability, lack of site specificity, and chemical instability. On the other hand, targeted prodrug design represents a new strategy for directed and efficient drug delivery. Particularly, targeting the prodrugs to a specific enzyme or a specific membrane transporter, or both, has potential as a selective drug delivery system in cancer chemotherapy or as an efficient oral drug delivery system. Site-selective targeting with prodrugs can be further enhanced by the simultaneous use of gene delivery to express the requisite enzymes or transporters. This review highlights evolving strategies in targeted prodrug design, including antibody-directed enzyme prodrug therapy, gene-directed enzyme prodrug therapy, and peptide transporter-associated prodrug therapy.
authors.affiliation: College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109-1065, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Han
authors.forename: G L
authors.initials: GL
authors.lastname: Amidon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001682:Biological Availability; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D007408:Intestinal Absorption; D007422:Intestines / Q000201:enzymology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D000074011:Peptide Transporter 1; D010455:Peptides / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D011355:Prodrugs / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D004798:Enzymes; D008565:Membrane Proteins; D000074011:Peptide Transporter 1; D010455:Peptides; D004364:Pharmaceutical Preparations; D011355:Prodrugs; C082186:SLC15A1 protein, human; D027981:Symporters; C093694:hydrogen-coupled oligopeptide transporter PepT2