Near-infrared-actuated devices for remotely controlled drug delivery.
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.
Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
Brian P
BP
Timko
Manuel
M
Arruebo
Sahadev A
SA
Shankarappa
J Brian
JB
McAlvin
Obiajulu S
OS
Okonkwo
Boaz
B
Mizrahi
Cristina F
CF
Stefanescu
Leyre
L
Gomez
Jia
J
Zhu
Angela
A
Zhu
Jesus
J
Santamaria
Robert
R
Langer
Daniel S
DS
Kohane
D000818:Animals; D016503:Drug Delivery Systems; D004867:Equipment Design; D007259:Infrared Rays; D046529:Microscopy, Electron, Transmission; D053761:Nanocomposites; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
diabetes; ethylcellulose; gold; nanoshell; poly(n-isopropylacrylamide)