SOLUBLE POLYMERS FOR LECTIN-MEDIATED DRUG TARGETING

Soluble polymers, including synthetic polymers and dextrans, show considerable physicochemical versatility that is vital in the development of useful drug targeting systems. Precise control over biodistribution kinetics, rates of plasma clearance, elimination and extravasation can help to optimise overall therapeutic index and biocompatibility. Dextrans and co-polymers based on N-(2-hydroxypropyl)methacrylamide (HPMA) substituted with either mannose or fucose interact competitively with receptors on peritoneal macrophages and Kupffer cells, while galactose-substituted materials can deliver large doses of drugs into hepatocytes in vivo. Entry into cells of drugs coupled to polymeric carriers is restricted to endocytic pathways, and drug-carrier linkages with controlled lysosomal degradation can provide a suitable cellular concentration profile, with minimal release outside the target cells. These approaches are particularly promising for the organ-specific therapy of liver cancer; however, receptor saturation is a potential problem that must be considered in designing any therapeutic protocol. Other applications of glycosylated polymers include competitive inhibition of premature scavenging of therapeutic proteins by liver lectins, and also targeting to lectins of non-hepatic tissues.