Dextrans for targeted and sustained delivery of therapeutic and imaging agents

Dextrans are glucose polymers which have been used for more than 50 years a s plasma volume expanders. Recently, however, dextrans have been investigat ed for delivery of drugs, proteins/enzymes, and imaging agents. These highl y water soluble polymers are available commercially as different molecular weights OM,) with a relatively narrow M-w, distribution. Additionally, dext rans contain a large number of hydroxyl groups which can be easily conjugat ed to drugs and proteins by either direct attachment or through a linker. I n terms of pharmacokinetics, the intact polymer is not absorbed to a signif icant degree after oral administration. Therefore, most of the applications of dextrans as macromolecular carriers are through injectable routes. Howe ver, a few studies have reported the potential of dextrans for site (colon) -specific delivery of drugs via the oral route. After the systemic administ ration, the pharmacokinetics of the conjugates of dextran with therapeutic/ imaging agents are significantly affected by the kinetics of the dextran ca rrier. Animal and human studies have shown that both the distribution and e limination of dextrans are dependent on the M-w, and charge of these polyme rs. Pharmacodynamically, conjugation with dextrans has resulted in prolonga tion of the effect, alteration of toxicity profile, and a reduction in the immunogenicity of drugs and/or proteins. A substantial number of studies on dextran conjugates of therapeutic/imaging agents have reported favorable a lteration of pharmacokinetics and pharmacodynamics of these agents. However , most of these studies have been carried out in animals, with only a few b eing extended to humans. Future studies should concentrate on barriers for the clinical use of dextrans as macromolecular carriers for delivery of dru gs, proteins, and imaging agents. (C) 2000 Elsevier Science B.V. All rights reserved.