PH-SENSITIVE HYDROGELS FOR DRUG RELEASE

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Development of guidelines for the design of pH-sensitive, swelling- controlled release systems for delivery of drugs, bimolecules and genetically-engineered molecules is investigated. The novel systems are produced from hydrophilic, ionic, glassy polymers which can swell in water or biological fluids. Mechanisms of water-soluble solute diffusion through initially glassy, continuously swelling hydrophilic polymer systems are investigated. Experimental studies are performed with crosslinked copolymers of 2-hydroxyethyl methacrylate with methacrylic acid, N-vinyl- pyrrolidone and various acrylamides using several solutes of low or high molecular weight. The effect of degree of crosslinking and dynamic swelling behavior of the polymer on solute diffusion are studied with a combination of diffusion/dissolution/microtoming/microscopy/stress relaxation experiments. The mesh size is determined experimentally by equilibrium swelling studies. Models are developed for the pH sensitivity of the degree of swelling and the dynamic swelling of these hydrogels.