Mechanics of controlled release of insulin entrapped in polyacrylic acid gels via variable electrical stimuli

Abstract

Controlled release insulin delivery systems possess multiple advantages over conventional ones, including maintaining desired blood glucose levels for prolonged periods and minimizing complications due to insulin overdose. Compared to other controlled-release mechanisms, electro-responsive polymers present the advantages of high controllability and ability to be coupled with microelectronics. This paper reports the possibility of using electro-responsive polyacrylic acid (PAA) and polymethacrylic acid (PMA) hydrogels for controlled delivery of insulin using intermittent electrical signals via matrix deformation. PAA hydrogels showed very good electrical responsivity under both constant and step current inputs, releasing up to 80% of protein at 10V stimulus, compared to 20% release in the absence of stimulus. Analysis of spatial variation under electrical stimuli suggested that release of protein is a combined effect of deformation of the hydrogel and electrophoresis of protein molecules. Binding interaction analysis revealed that insulin entrapment is largely due to hydrogen bonding between the polymer matrix and insulin, and flooding the matrix with electrical charge likely disrupts the attractive forces that kept protein in place helping the release of the proteins. Understanding the molecular interactions affecting insulin retention and release mechanisms of PAA hydrogels is useful for developing and optimizing hydrogel-based controlled drug release systems.