Stimuli-sensitive hydrogels were investigated for application in developing dynamically responsive drug delivery systems and glucose sensors. The effect of hydrogel chemistry on physicochemical properties was studied in three different systems.; In the first system, the role of hydrogel hydrophobicity on the volume transition pH (VT pH) of pH-sensitive copolymer hydrogels based of N-isopropylacrylamide (NIPA) and alpha-alkylacrylic acid (RAA) was studied. These hydrogels are being developed for incorporation into a hydrogel/enzyme based drug delivery device for autonomous, rhythmic delivery of Gonadotropin Releasing Hormone (GnRH). We show that increasing the hydrogel hydrophobicity by copolymerizing NIPA with higher homologs of RAA affects remarkable alkaline shifts in VT pH. Membranes separating solutions of glucose and glucose oxidase in a device prototype exhibit pH-oscillations over ranges that become increasingly alkaline with progressive hydrophobicity.; In the second hydrogel system, conventional organic tetrafunctional crosslinkers were replaced by nanoclay crosslinking elements. These hydrogels exhibit much improved mechanical and optical properties compared to organically crosslinked hydrogels, due to multifunctionality of the clay platelets and the homogeneous nature of the network. While previous investigators have only been able to use this strategy to strengthen temperature-sensitive hydrogels, we showed that pH-sensitivity can be achieved by modifying the synthesis strategy, and by using charge modifiers such as pyrophosphates, which overcome the flocculating tendency of the clay particles during copolymerization of NIPA with acidic comonomers.; In the third system, we investigated particular mechanical and swelling properties hydrogels containing phenylboronic acid (PBA) sidegroups. At pH > pKa of PBA (∼8.6), these hydrogels exhibit reversible glucose-mediated crosslinking, which causes gel deswelling and increase in gel modulus. By incorporating a tertiary amino sidegroup in some of the hydrogel sidechains, reversible crosslinking was shown to occur at pH 7.4. Since the crosslinking phenomenon is unique to glucose, physiologically relevant, enzyme-free glucose-specific sensors based on these hydrogels now appear feasible.; Keywords. Hydrogel, pH-sensitive, N-isopropylacrylarnide, alkylacrylic acid, pulsatile drug delivery, hydrophobicity, swelling hysteresis, nanoclay, mechanical strength, crosslinking, glucose-sensitive, phenylboronic acid, sensor, compression modulus, dynamic mechanical analysis, storage modulus.
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