Dynamically bonded layer-by-layer films for self-regulated insulin release

Abstract

Layer-by-layer assembled films using reversible/dynamic bonds between the polymer pairs as driving forces are dynamic in nature. They may disintegrate under certain conditions as a result of the breakage of the dynamic bonds. More importantly they disintegrate gradually under conditions of equilibrium control, making them suitable for sustained drug release. Here insulin release from dynamic LbL films was demonstrated as an example. The films were fabricated from a fluorescently-labeled insulin–PVA (PVA: polyvinyl alcohol) conjugate and poly[acrylamide-co-3-(acrylamido)-phenylboronic acid], using a reversible covalent bond, i.e., phenylboronate ester bond, as the driving force. Film fabrication was followed by UV-vis and fluorescence spectroscopy. In all cases linear film growth was observed. The film growth rate increases with decreasing pH and increasing ionic strength of the assembly solutions. Successful integration of insulin into the films was achieved by covalent conjugation of insulin with PVA. When immersed in an aqueous solution, the films disintegrate gradually, thus releasing insulin into the media. Insulin release rate increases with increasing pH and decreasing ionic strength of the media. More importantly, it increases with increasing glucose concentration in the media. The glucose response of the film was attributed to the conversion of PBA (PBA: phenylboronic acid) groups in the film from a neutral form to a negatively charged one as a result of the formation of glucose–PBA complexes, thus increasing the rate of the film disintegration.