Potential of Sugar Residues Attached to N-(2- Hydroxypropyl)methacryl amide Copolymers as Targeting Groups for the Selective Delivery of Drugs

Abstract

Soluble copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) have already shown potential as targetable drug-carriers. Here HPMA copolymers were synthesized which contained N-linked aminosugars attached to the poly mer backbone via a diglycyl side-chain. Following radioiodination their body distribution in rats was investigated. Incorporation of mannosamine or glu cosamine caused enhanced deposition in liver macrophages following intra venous and intraperitoneal administration, and increased retention at the site of injection when the carrier was administered subcutaneously. Macrophage pinocytic uptake of certain HPMA copolymers was also assessed using rat peri toneal macrophages cultured in vitro. It was demonstrated that polymers bear ing mannosamine or glucosamine are internalized rapidly by a common recep tor and that the interaction can be inhibited by free D-mannose, L-fucose, but not by D-glucose.