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 obvia...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2014
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| Online Access: | http://hdl.handle.net/1721.1/89122 https://orcid.org/0000-0002-7958-8980 https://orcid.org/0000-0001-5409-5808 https://orcid.org/0000-0003-0525-9479 https://orcid.org/0000-0003-4255-0492 |
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| author | Timko, Brian P. Arruebo, Manuel Shankarappa, Sahadev A. McAlvin, J. Brian Okonkwo, Obiajulu Stephanie Mizrahi, Boaz Stefanescu, Cristina F. Gomez, Leyre Zhu, Jia Santamaria, Jesus Zhu, Angela W. Langer, Robert S Kohane, Daniel S |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Timko, Brian P. Arruebo, Manuel Shankarappa, Sahadev A. McAlvin, J. Brian Okonkwo, Obiajulu Stephanie Mizrahi, Boaz Stefanescu, Cristina F. Gomez, Leyre Zhu, Jia Santamaria, Jesus Zhu, Angela W. Langer, Robert S Kohane, Daniel S |
| author_sort | Timko, Brian P. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:22:00Z |
| format | Article |
| id | mit-1721.1/89122 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:22:00Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/891222022-09-29T14:30:28Z Near-infrared-actuated devices for remotely controlled drug delivery Timko, Brian P. Arruebo, Manuel Shankarappa, Sahadev A. McAlvin, J. Brian Okonkwo, Obiajulu Stephanie Mizrahi, Boaz Stefanescu, Cristina F. Gomez, Leyre Zhu, Jia Santamaria, Jesus Zhu, Angela W. Langer, Robert S Kohane, Daniel S Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Chemistry Koch Institute for Integrative Cancer Research at MIT Timko, Brian P. Okonkwo, Obiajulu Stephanie Mizrahi, Boaz Zhu, Jia Zhu, Angela Langer, Robert Kohane, Daniel S. 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. National Institutes of Health (U.S.) (Grant GM073626) Massachusetts Institute of Technology. Laser Biomedical Research Center (Sanofi Aventis (Firm) Biomedical Innovation Funding Award) National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award National Institutes of Health (U.S.) (Grant F32GM096546) 2014-09-02T13:57:05Z 2014-09-02T13:57:05Z 2014-01 2013-10 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/89122 Timko, B. P., M. Arruebo, S. A. Shankarappa, J. B. McAlvin, O. S. Okonkwo, B. Mizrahi, C. F. Stefanescu, et al. “Near-Infrared-Actuated Devices for Remotely Controlled Drug Delivery.” Proceedings of the National Academy of Sciences 111, no. 4 (January 28, 2014): 1349–1354. https://orcid.org/0000-0002-7958-8980 https://orcid.org/0000-0001-5409-5808 https://orcid.org/0000-0003-0525-9479 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1073/pnas.1322651111 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Timko, Brian P. Arruebo, Manuel Shankarappa, Sahadev A. McAlvin, J. Brian Okonkwo, Obiajulu Stephanie Mizrahi, Boaz Stefanescu, Cristina F. Gomez, Leyre Zhu, Jia Santamaria, Jesus Zhu, Angela W. Langer, Robert S Kohane, Daniel S Near-infrared-actuated devices for remotely controlled drug delivery |
| title | Near-infrared-actuated devices for remotely controlled drug delivery |
| title_full | Near-infrared-actuated devices for remotely controlled drug delivery |
| title_fullStr | Near-infrared-actuated devices for remotely controlled drug delivery |
| title_full_unstemmed | Near-infrared-actuated devices for remotely controlled drug delivery |
| title_short | Near-infrared-actuated devices for remotely controlled drug delivery |
| title_sort | near infrared actuated devices for remotely controlled drug delivery |
| url | http://hdl.handle.net/1721.1/89122 https://orcid.org/0000-0002-7958-8980 https://orcid.org/0000-0001-5409-5808 https://orcid.org/0000-0003-0525-9479 https://orcid.org/0000-0003-4255-0492 |
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