A reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time. Despite the clear clinical need for a device that meets these criteria, none has been reported to date to our knowledge. To address this deficiency, we developed an implantable reservoir capped by a nanocomposite membrane whose permeability was modulated by irradiation with a near-infrared laser. Irradiated devices could exhibit sustained onstate drug release for at least 3 h, and could reproducibly deliver short pulses over at least 10 cycles, with an on/off ratio of 30. Devices containing aspart, a fast-acting insulin analog, could achieve glycemic control after s.c. Implantation in diabetic rats, with reproducible dosing controlled by the intensity and timing of irradiation over a 2-wk period. These devices can be loaded with a wide range of drug types, and therefore represent a platform technology that might be used to address a wide variety of clinical indications.
B. P. Timko, Arruebo, Md, Dr. Sahadev Shankarappa, McAlvin, J. B., Okonkwo, O. S., Mizrahi, B., Stefanescu, C. F., Gomez, L., Zhu, J., Zhu, A., Santamaria, J., Langer, R., and Kohane, D. S., “Near-Infrared-Actuated Devices for Remotely Controlled Drug Delivery”, Proceedings of the National Academy of Sciences of the United States of America, vol. 111, pp. 1349-1354, 2014.