Pulsatile release from a flat self-oscillating chitosan macrogel

Coupling oscillatory chemical reactions to smart materials which can respond to external stimuli is considered an answer to the long-standing issue of pulsatile drug delivery. Although a number of coupled architectures exist, there are no systems reporting pH-controlled pulsed drug release based on chemical oscillators. In this paper, we report for the first time a proof-of-concept self-oscillatory chitosan macrogel, employing the palladium-catalysed oxidative carbonylation reaction as the driving force of its oscillations. The reported hydrogel is composed of highly biocompatible components and a novel imine-functionalised chitosan-palladium catalyst with zero leaching rates. This macrogel was shown to rhythmically release not only the products of the reaction, but also fluorescein, which is used as an FDA-approved model drug. The step-wise release pattern corresponded to the step-wise dynamics of pH decrease in methanol:water, while in pure methanol, the changes in pH had an oscillatory mode, accompanied by mirrored oscillations in fluorescein concentration. This proof-of-concept system significantly expands the horizons of pulsatile delivery materials for future research.