Engineering the Nonmorphing Point of Actuation for Controlled Drug Release by Hydrogel Bilayer across the pH Spectrum

Hydrogel-based pH-responsive bilayer actuators exhibit bidirectional actuation due to the differences in the concentration gradient developed across the thickness, the volume expansion due to swelling, and the mechanical stiffness of the layers involved. At a pH value (point), where the sum of these factors generates moments of equal magnitudes, the moments cancel each other and result in no net actuation. This pH point is termed here as a "nonmorphing point". In this work, we present a bilayer of chitosan (CS) and carboxymethyl cellulose (CMC) cross-linked with citric acid (CA) with tunable nonmorphing points across the pH spectrum by modulating the concentration and cross-linking density of the layers involved. The standard CS/CMC bilayer films took about 40 s to completely fold (clockwise) in 0.1 M HCl and 78 s to completely fold (anticlockwise) in 0.1 M NaOH. Generally, pH-responsive actuators are designed for targeted drug delivery to a specific site inside the body as they show bidirectional (clockwise/anticlockwise) actuation around a single nonmorphing point. The same pH-responsive system cannot be applied for drug release at another site with a different functioning pH. Thus, having a pH-responsive system with multiple nonmorphing points is highly desirable. Drug release experiments were performed with FITC and EtBr as model drugs loaded in CS and CMC layers. Moreover, the clockwise/anticlockwise actuation of the bilayer around the nonmorphing point can facilitate or inhibit the release of a drug. The clockwise actuation resulted in 55% FITC release and inhibited EtBr release to 4%; anticlockwise actuation resulted in 50% EtBr release and inhibited FITC release to 5%. We demonstrated morphing induced drug release by hydrogel bilayer films with tunable nonmorphing points across the pH spectrum.