Controlled-release of drugs from cross-linked polymers containing cubane as a crosslinking agent

Two anti-inflammatory drugs, indomethacin and aspirin together with cubane-1, 4-dicarboxylic acid (CDA) were covalently linked with 2-hydroxyethyl methacrylate (HEMA). The drug-linked HEMA (indomethacin-linked HEMA) is abbreviated as HI, aspirin-linked HEMA as HA and cubane-1, 4-dicarboxylic acid (CDA) linked to two HEMA group is the cross-linking agent (CA). A difunctional spacer group was introduced between the drugs and acrylic moiety of the monomer through a hydrolyzable ester linkage. Free radical cross-linking polymerization of the monomers with drug effect was carried out in dioxane solution at various CA ratios, using AIBN as initiator in the temperature range 60-70°C. The compositions of the cross-linked three-dimensional polymers were determined by FT-IR spectroscopy. The glass transition temperature (Tg) of the network polymers was determined calorimetrically. The hydrolysis of drug-polymer conjugates was carried out in cellophane membrane dialysis bags containing an aqueous buffer solution (pH 8 and pH 1) at 37°C. Detection of the hydrolysis product by UV spectroscopy shows that the drugs were released by hydrolysis of the ester bond located between the drug and spacer group.