Dextrans for targeted and sustained delivery of therapeutic and imaging agents

Abstract

Dextrans are glucose polymers which have been used for more than 50 years as plasma volume expanders. Recently, however, dextrans have been investigated for delivery of drugs, proteins/enzymes, and imaging agents. These highly water soluble polymers are available commercially as different molecular weights (M(W)) with a relatively narrow M(W) distribution. Additionally, dextrans contain a large number of hydroxyl groups which can be easily conjugated to drugs and proteins by either direct attachment or through a linker. In terms of pharmacokinetics, the intact polymer is not absorbed to a significant degree after oral administration. Therefore, most of the applications of dextrans as macromolecular carriers are through injectable routes. However, a few studies have reported the potential of dextrans for site (colon)-specific delivery of drugs via the oral route. After the systemic administration, the pharmacokinetics of the conjugates of dextran with therapeutic/imaging agents are significantly affected by the kinetics of the dextran carrier. Animal and human studies have shown that both the distribution and elimination of dextrans are dependent on the M(W) and charge of these polymers. Pharmacodynamically, conjugation with dextrans has resulted in prolongation 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 alteration of pharmacokinetics and pharmacodynamics of these agents. However, most of these studies have been carried out in animals, with only a few being extended to humans. Future studies should concentrate on barriers for the clinical use of dextrans as macromolecular carriers for delivery of drugs, proteins, and imaging agents.