I-18: A Macromolecular Prodrug Approach for Selective Delivery of Immunosuppressants for Liver Transplantation
New and innovative methods of delivery of therapeutic agents using polysaccharide as carriers have been recently developed, which target site of action, increase the intensity and/or prolong pharmacologic action, and/or reduce toxicity of small molecule drugs, proteins, or enzymes. The physicochemical properties of these carriers, including molecular weight (MW), electric charge, chemical modifications, and degree of polydispersity and/or branching would significantly affect in vivo disposition and pharmacodynamic profiles of drugs that are carried by these macromolecules. In this talk, development of dextran-methylprednisolone conjugates with different linkers between the macromolecule (dextran) and methylprednisolone will be discussed in terms its potential effect for selective delivery in liver transplantation and ischemiareperfusion associated with the procedure. Specifically, effects of the physicochemical characteristics of the dextran carrier and the type of the linker on the pharmacokinetics and pharmacodynamics of the conjugates will be discussed. These studies demonstrate the importance of pharmacokinetic considerations in the design and pharmacodynamics of polysaccharidebased macromolecular prodrugs.