Abstract
AbstractAn experimental study was conducted to determine the mechanisms of transport for delivery of cardiovascular agents using a pH-sensitive hydrogel as the carrier. Copolymer gels based on hydrophilic (2-hydroxyethyl methacrylate) and polybasic (N,N-diethylaminoethyl methacrylate) monomers were formed as membranes and analyzed for their potential to control the diffusion of model solutes as well as heparin and streptokinase. The polybasic materials were selected because they would allow drug delivery to be triggered by microenvironmental pH fluctuations around the site of a blood clot. In slightly basic solutions, the polymers remained in a thermodynamic state of phase-separation, while the polymer absorbed more solution and the mesh size increased once the pH was less than the pKb of the polybasic moiety. The hydrogels' equilibrium swelling ratios were determined as a function of pH, and the mesh sizes were determined by rubber elasticity measurements. Diffusion of model solutes, as well as heparin, was studied using side-by-side diffusion cells to determine the influence of gel morphology and mesh size on the screening of the solutes. Streptokinase release from these gels was modulated by environmental pH.
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