Electroresponsive pulsatile depot delivery of insulin from poly(dimethylaminopropylacrylamide) gel in rats

We describe a model for pulsatile drug delivery with an electroresponsive polymer that is stimulated by an externally applied electrical field. Insulin loaded in an electroresponsive poly(dimethylaminopropylacrylamide) (PDMAPAA) gel was administered as a subcutaneous depot in rats. The gel induced a pulsatile plasma glucose decrease in correspondence to stimulation with a constant current of 1.0 mA (0.36 mA/cm2). The first drop occurred at 0.5 h after a 1-min application of current at 0 h and the second drop occurred at 3 h after a 10-min application of current at 2 h. Calculation of pharmacological bioavailability showed that the gel released 0.12% of the loaded insulin after these two stimuli. This in vivo study demonstrates the feasibility of this pulsatile delivery system. The mechanism of insulin release from the electroresponsive PDMAPAA gel is associated with electrokinetic flow of solvated insulin with water; that is, transportation process of counterions (electrophoresis) and water molecules (electroosmosis) in the crosslinked polyelectrolyte gel network.