Pulsatile release of insulin via photothermally modulated drug delivery

Composites of thermally-sensitive hydrogels and optically-active nanoparticles have been developed for transdermal photothermally modulated drug delivery. Copolymers of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) exhibit a lower critical solution temperature (LCST) that is slightly above body temperature. Gold-gold sulfide nanoshells have been incorporated into poly(NIPAAm-co-AAm) hydrogels to initiate a temperature change with light. The nanoshells heat upon irradiation at their peak absorption wavelength, causing the collapse of the polymer and the subsequent release of any drug contained within the polymer matrix. For this to occur, the light must pass through the skin and retain enough power to cause significant heating in the nanoshells. Light between 800 and 1200 nm has been shown to have relatively lour levels of attenuation in tissue. Composite polymers of the nanoshells and NIPAAm-co-AAm can deliver controlled pulsatile doses of insulin in response to near-IR irradiation. The activity of the released insulin was determined by measuring glucose uptake by adipocytes that had been exposed to photothermally released insulin. The released insulin did not show a loss in activity as compared to the positive control (insulin in saline), thus demonstrating transdermal photothermally modulated drug deliver in vitro.