Despite myriad challenges, clinicians see room for progress.
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Contributed by Robert Langer, December 6, 2013 (sent for review October 23, 2013)
Significance
Devices that release a drug in response to a remote trigger would enable on-demand control of the timing and dose of drug released. They would allow the patient or physician to adjust therapy precisely to a target effect, thus improving treatment and reducing toxicity. We have developed implantable reservoirs that release a drug when irradiated with near-infrared laser light. The release rate was correlated to laser intensity, with negligible leakage between doses. Devices containing aspart, a fast-acting analog of insulin, were implanted in diabetic rats and were able to achieve glycemic control upon irradiation. Such devices can be loaded with a wide range of drugs to treat a variety of clinical indications.
Abstract
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 on-state 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.
Footnotes
↵1B.P.T. and M.A. contributed equally to this work.
- ↵2To whom correspondence may be addressed. E-mail: rlanger{at}mit.edu or daniel.kohane{at}childrens.harvard.edu.
Author contributions: B.P.T., M.A., S.A.S., J.S., and D.S.K. designed research; B.P.T., M.A., S.A.S., J.B.M., O.S.O., B.M., C.F.S., L.G., J.Z., and A.Z. performed research; B.P.T., M.A., S.A.S., J.B.M., O.S.O., J.S., R.L., and D.S.K. analyzed data; and B.P.T., M.A., J.S., R.L., and D.S.K. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1322651111/-/DCSupplemental.
Light-controlled devices for remote drug delivery
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