Reversible adsorption by a pH- and temperature-sensitive acrylic hydrogel

Thermo- and pH-sensitive hydrogels were synthesized using N-isopropylacrylamide (NIPA) and N-amino-propylmethacrylamide, cross-linked with N,N'-methylenebis(acrylamide). The dependence of the degree of swelling on the cross-linking density was analyzed according to the Flory-Huggins theory and a master curve obtained. To optimize the efficiency of these hydrogels in controlled release, we studied the loading and release of a divalent molecule (naphthalenedisulfonic acid, NS-2) in media of different ionic strengths and pH. The uptake process followed the Langmuir adsorption isotherm model. The highest loading occurred when the amino groups in the get were protonated (acidic pH) and could come close each other to form a binding site for the two sulfonic groups of NS-2. i.e. low degree of cross-linking and collapsed state. Below the phase transition temperature (33 degreesC). NS-2 loaded hydrogels quickly released a significant amount of adsorbate until a now equilibrium between free NS-2 and adsorbed NS-2 was achieved. Above that temperature, hydrogels not only stopped the release but were even able to take free NS-2 up again from the medium, showing that the loading/release process was reversible and reproducible after several temperature cycles. At 37 degreesC the release rate was independent of the degree of cross-linking (NIPA caused the hydrogel to collapse). but was strongly affected by the pH and salt concentrations of the medium, which condition the strength of the interaction between the hydrogel amino groups and the NS-2 sulfonic groups. In an acidic medium, the protonated amino groups bind NS-2 strongly and the amount released is small. In contrast, at pH 7.4 or in the presence of a high salt concentration, the hydrogel loses its affinity for NS-2 and the release rate increases, giving pH- or salt-sensitive delivery systems. Additionally, since the hydrogel is collapsed. the release can be prolonged for a long period of time. (C) 2002 Elsevier Science B.V. All rights reserved.