Binding and release studies of a cationic drug from a star-shaped four-arm poly(ethylene oxide)-b-poly(methacrylic...

Star-shape polymers possess higher densities of terminal functional groups and three-dimensional tetrahedron structure that induce significantly different association and interactions with drug compared to linear structure of identical molecular weights. Four-arm poly(ethylene oxide)-b-poly(methacrylic acid) block copolymer was synthesized by atom transfer radical polymerization technique, and it self-assembled into core-shell micelles and extended unimers at low and high pH respectively. The negatively charged carboxylate groups on the polymer chains interacted with a cationic drug through electrostatic interaction forming polymer/drug complexes stabilized by biocompatible hydrophilic PEO segments. The hydrodynamic radius (R(h)) of the polymeric aggregates and polymer/drug complexes ranged from 46 to 84 nm and 32 to 55 nm at pH of 4.6 and 8.0 respectively, making them suitable for drug delivery applications. The thermodynamic parameters and interactions between polymer and drug were determined by isothermal titration calorimetric technique. The electrostatic force, hydrogen bonding and hydrophobic interactions controlled the characteristics of polymer/drug formation and complexes when the molar ratios of drug and polymer were varied. Drug selective electrode system was used to measure the dynamic release of imipramine hydrochloride (IPH) from multi-arm PEO-b-PMAA star polymer. The release exponent n was greater than 0.5 indicating a non-Fickian type diffusion behavior, where the release behavior was dominated by chain relaxation induced by ion exchange that was dependent on pH.