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

A novel polymer complex system sensitive to glucose was studied as a c andidate material for formulating a chemically regulated insulin deliv ery system. A phenylboronic acid (PBA) moiety was incorporated in poly (N-vinyl-2-pyrrolidone) [poly(NVP-co-PBA)] as a glucose sensor molecu le by the radical copolymerization of N-vinyl-2-pyrrolidone with m-acr ylamidophenylboronic acid. Complex formation as well as dissociation w as estimated by viscosity changes in the complex solution. A positive viscosity change was observed for the poly(vinyl alcohol) (PVA)/poly(N VP-co-PBA) complex system due to complex formation between PVA diol un its and poly(NVP-co-PBA) boronate units; minimal or no change in visco sity was observed for either PVA/boric acid or PVA/poly(NVP). The visc osity of the PVA/poly(NVP-co-PBA) system is able to be controlled thro ugh 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 int eraction was further investigated by following decreased complex visco sity with the addition of a competitive polyol: glucose, tris(hydroxym ethyl)aminomethane (TRIS) or (+/-)-3-amino-1,2-propanediol (APD). The viscosity decreased steeply when glucose was added while minimal chang e in viscosity was observed when either TRIS or APD was added. This su ggested that the chemical structure of the diol compound had an import ant role in exchange with the diol-boronate complex. These results poi nt to the promising use of PVA/poly(NVP-co-PBA) complex systems in the development of a novel glucose responsive insulin release system.