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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Arruebo, Manuel Timko, Brian P. Mcalvin, J. Brian Gomez, Leyre Mizrahi, Boaz Langer, Robert Santamaria, Jesus Zhu, Jia Zhu, Angela Shankarappa, Sahadev A. Okonkwo, Obiajulu S. Stefanescu, Cristina F. Kohane, Daniel S. |
| Description | Author Affiliation: Timko BP ( Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 4 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Drug Delivery Systems Infrared Rays Animals Equipment Design Microscopy, Electron, Transmission Nanocomposites Rats, Sprague-Dawley Reproducibility Of Results Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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