Glucose-powered pulsatile release

Abstract

Pulsatile release is required for many drugs from hormones to vaccines, but automating this release typically requires elaborate pumping systems with electronic controls and transcutaneous catheters. This paper describes a materials-based approach to this functionality, using a combination of composite polymer membranes to provide discrete pulses of drug at preprogrammed intervals using only a static concentration of glucose in water. Drug is encapsulated in acid-sensitive polymer membranes. Enzymes which convert glucose to acid are immobilized in other polymer membranes, along with sacrificial acid scavengers. These membranes are stacked alternately into a polymer laminate and sealed around the bottom and edges. Glucose diffuses steadily into the top membrane and is converted to acid. This acid is consumed by the scavenger until the scavenger is exhausted, at which point it triggers the acid-sensitive drug membrane below. That membrane swells and delaminates from the stack, releasing its payload, and the process repeats, potentially with different drugs in each layer and different preprogrammed delay times between each dose. This paper provides the first experimental demonstration of such a system, characterizes its components, models the system computationally, and provides basic design rubrics for further development.