In the field of controlled release, constant rate of zero order delivery of drugs is often considered to be the gold standard. This philosophy reflects the notion that drug effect is directly related to the instantaneous concentration of drug in an appropriate biosphere.
However, in recent decades evidence has accumulated that certain clones of drugs particularly hormones are best administered with a periodic pulsatile program. Such a program will mimic the normal endogenous pattern of hormone release from endocrine glands. In fact, hormone replacement therapy using zero order delivery has been shown to fail in some cases with the target endocrine fraction restored only when the normal pulsatile pattern of release is imitated by the delivery system.
Research workers then geared towards developing an implantable, autonomously pulsing drug delivery system which can be used for such hormones and whose pulse pattern is controlled by device design. No external energy source, such as electricity, magnetism or heat is required to activate the system.
The system is based on a cross-linked poly (N-isopropyl acrylamide - co - methacrylic acid) hydrogel (HG) and the enzyme glucose oxidase (GO). GO is situated in a chamber and communicates with body fluids through the HG membrane. Glucose, at constant activity in the body permeates through the HG and causes the latter to collapse by neutralizing pendant carboxylic acid groups.
By this means, glucose permeation is sharply reduced, and is subsequent proton production. Eventually the protons are released from the HG membrane and the latter re-swells, restoring glucose permeability. This process can be repeated indefinitely, provided the system maintains its integrity and the external glucose concentration remains constant. Drug release from the chamber will follow the pulsatile swelling of membrane.