Drug Delivery with Protein and Peptide Carriers

  • John M. Whiteley


Drugs or toxins such as methotrexate, adriamycin, daunomycin, fluorodeoxyuridine, neocarzinostatin, and ricin can be bound, either covalently or by occlusion, to proteins, synthetic polypeptides, and antibodies. Common reactions for coupling these drugs to carriers include the use of carbodiimides, the generation of Schiff bases followed by reduction, and the formation of disulfide linkages. Often a spacer group such as a dextran or polypeptide is included to facilitate the interaction. The resultant conjugates usually contain from approximately 5 to 25 mol of drug per mole of carrier and most retain attenuated antimetabolic properties typical of the free drug. The complexes, however, also possess the properties of the carrier, and in this way delivery and uptake of a bound drug by cells can be significantly different from that of the free drug. For example, in vivo, the higher molecular weight of the conjugate can lead to a larger retention time for the drug prior to excretion, with the attendant greater opportunity for interaction with target cells. Additionally, the mechanism by which the drug is taken up into a cellular target may be altered for the drug-carrier complex and, in the case of an antibody carrier, tissue specificity may also be added to the properties of the drug. These and other characteristics of the complexes are discussed in detail in the text and their possible relevance to chemotherapy is outlined.


Free Drug Folinic Acid Dihydrofolate Reductase Diphtheria Toxin Divinyl Ether 
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© Plenum Press, New York 1985

Authors and Affiliations

  • John M. Whiteley
    • 1
  1. 1.Division of Biochemistry, Scripps Clinic and Research FoundationDepartment of Basic and Clinical ResearchLa JollaUSA

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