Regulation of Controlled Release of Ibuprofen from Crosslinked Polymers Containing Cubane as a New Crosslinking Agent

Abstract

The nonsteroidal anti-inflammatory drug 2-(4-isobutylphenyl)-propionic acid (ibuprofen) and cubane-1,4-dicarboxylic acid (CDA) were covalently linked with 2-hydroxyethyl methacrylate (HEMA). The drug-linked HEMA (ibuprofen-linked HEMA) abbreviated as HI and cubane-1,4-dicarboxylic acid (CDA) linked to two HEMA groups as CA. A difunctional spacer group was introduced between the drug and acrylic moiety of the monomer through a hydrolyzable ester linkage. Free radical crosslinking polymerization of the monomer HI with the various ratios CA as crosslinking agent were carried out in DMF, DMSO or dioxane solution, using AIBN as initiator at the temperature range of 60-70°C. The structure of the monomers was confirmed by FTIR, ¹H NMR and ¹³C NMR spectroscopy. The compositions of the crosslinked three-dimensional polymers were determined by FTIR spectroscopy. 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 drug (ibuprofen) was released by the hydrolysis of the ester bond located between the drug and spacer group.

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