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Targeted prodrug design to optimize drug delivery

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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, genedirected enzyme prodrug therapy, and peptide transporter-associated prodrug therapy.

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  1. Parke-Davis Pharmaceutical Research, Division of Warner-Lambert, Department of Pharmacokinetics, Dynamics and Metabolism, 2800 Plymouth Road, 48105, Ann Arbor, Michigan, USA

    Hyo-Kyung Han

  2. College of Pharmacy, The University of Michigan, 48109-1065, Ann Arbor, MI

    Gordon L. Amidon

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  1. Hyo-Kyung Han
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  2. Gordon L. Amidon
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Correspondence to Gordon L. Amidon.

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published March 21. 2000.

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Han, HK., Amidon, G.L. Targeted prodrug design to optimize drug delivery. AAPS PharmSci 2, 6 (2000). https://doi.org/10.1208/ps020106

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