Layer-by-layer deposited nano- and micro-assemblies for insulin delivery: A review

We present an overview of the recent progress in the development of layer-by-layer (LbL) assembled thin films and microcapsules for insulin delivery. The LbL deposition of insulin-containing thin films on the surfaces of flat substrates or microparticles has been investigated for orally administered insulin formulations. The amount of insulin in the LbL films can be precisely controlled by altering the number of layers in the films. As-prepared LbL films and microcapsules can be loaded with insulin by exposing the films and microcapsules to an insulin solution. The insulin can be released by pH-induced decomposition or permeability changes in the LbL films and microcapsules. Closed-loop insulin delivery systems that can release insulin in response to changes in glucose concentration have also been constructed with LbL films and microcapsules. Glucose-sensitive materials, such as glucose oxidase, concanavalin A, and phenylboronic acid, have been incorporated into insulin-containing LbL assemblies. In addition, LbL film-coated pancreatic islet cells have recently been developed as a bio-artificial pancreas, in which the islet cells are isolated from the recipient's immune system by the LbL coatings. Thus, LbL films and microcapsules could make a significant contribution to the further development of patient-friendly insulin delivery systems.