Shigeru Kitano

A novel drug delivery system utilizing a glucose responsive polymer complex between poly (vinyl alcohol) and poly (N-vinyl-2-pyrrolidone) with a phenylboronic acid moiety

Abstract A novel polymer complex system sensitive to glucose was studied as a candidate material for formulating a chemically regulated insulin delivery system. A phenylboronic acid (PBA) moiety was incorporated in poly(N-vinyl-2-pyrrolidone) [poly(NVP-co-PBA) ] as a glucose sensor molecule by the radical copolymerization of N-vinyl-2-pyrrolidone with m-acrylamidophenylboronic acid. Complex formation as well as dissociation was estimated by viscosity changes in the complex solution. A positive viscosity change was observed for the poly (vinyl alcohol) (PVA)/poly(NVP-co-PBA) complex system due to complex formation between PVA diol units and poly(NVP-co-PBA) boronate units; minimal or no change in viscosity was observed for either PVA/boric acid or PVA/poly(NVP). The viscosity of the PVA/poly(NVP-co-PBA) system is able to be controlled through changes in polymer molecular weight and/or polymer concentration. The maximum point in viscosity was observed at a molar ratio of PVA to poly (NVP-co-PBA) of 4:1 in this system. The diol-boronate complex interaction was further investigated by following decreased complex viscosity with the addition of a competitive polyol: glucose, tris(hydroxymethyl)aminomethane (TRIS) or (±)-3-amino-1,2-propanediol (APD). The viscosity decreased steeply when glucose was added while minimal change in viscosity was observed when either TRIS or APD was added. This suggested that the chemical structure of the diol compound had an important role in exchange with the diol-boronate complex. These results point to the promising use of PVA/poly(NVP-co-PBA) complex systems in the development of a novel glucose responsive insulin release system.