Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes

Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. T...

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Main Authors: Shankarappa, Sahadev A., Rwei, Alina Y, Lee, Jung-Jae, Zhan, Changyou, Liu, Qian, Ok, Meryem T., Langer, Robert S, Kohane, Daniel S
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: National Academy of Sciences (U.S.) 2017
Online Access:http://hdl.handle.net/1721.1/110515
https://orcid.org/0000-0001-6080-579X
https://orcid.org/0000-0001-8081-5143
https://orcid.org/0000-0002-0247-2875
https://orcid.org/0000-0003-4255-0492
https://orcid.org/0000-0003-0525-9479
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author Shankarappa, Sahadev A.
Rwei, Alina Y
Lee, Jung-Jae
Zhan, Changyou
Liu, Qian
Ok, Meryem T.
Langer, Robert S
Kohane, Daniel S
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Shankarappa, Sahadev A.
Rwei, Alina Y
Lee, Jung-Jae
Zhan, Changyou
Liu, Qian
Ok, Meryem T.
Langer, Robert S
Kohane, Daniel S
author_sort Shankarappa, Sahadev A.
collection MIT
description Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. The liposomes contained tetrodotoxin (TTX), which has ultrapotent local anesthetic properties. They were made photo-labile by encapsulation of a NIR-triggerable photosensitizer; irradiation at 730 nm led to peroxidation of liposomal lipids, allowing drug release. In vitro, 5.6% of TTX was released upon NIR irradiation, which could be repeated a second time. The formulations were not cytotoxic in cell culture. In vivo, injection of liposomes containing TTX and the photosensitizer caused an initial nerve block lasting 13.5 ± 3.1 h. Additional periods of nerve block could be induced by irradiation at 730 nm. The timing, intensity, and duration of nerve blockade could be controlled by adjusting the timing, irradiance, and duration of irradiation. Tissue reaction to this formulation and the associated irradiation was benign.
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spelling mit-1721.1/1105152022-10-01T10:08:09Z Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes Shankarappa, Sahadev A. Rwei, Alina Y Lee, Jung-Jae Zhan, Changyou Liu, Qian Ok, Meryem T. Langer, Robert S Kohane, Daniel S Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Materials Science and Engineering Koch Institute for Integrative Cancer Research at MIT Rwei, Alina Y Lee, Jung-Jae Zhan, Changyou Liu, Qian Ok, Meryem T. Langer, Robert S Kohane, Daniel S Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. The liposomes contained tetrodotoxin (TTX), which has ultrapotent local anesthetic properties. They were made photo-labile by encapsulation of a NIR-triggerable photosensitizer; irradiation at 730 nm led to peroxidation of liposomal lipids, allowing drug release. In vitro, 5.6% of TTX was released upon NIR irradiation, which could be repeated a second time. The formulations were not cytotoxic in cell culture. In vivo, injection of liposomes containing TTX and the photosensitizer caused an initial nerve block lasting 13.5 ± 3.1 h. Additional periods of nerve block could be induced by irradiation at 730 nm. The timing, intensity, and duration of nerve blockade could be controlled by adjusting the timing, irradiance, and duration of irradiation. Tissue reaction to this formulation and the associated irradiation was benign. National Institutes of Health (U.S.) (GM073626) 2017-07-07T13:25:36Z 2017-07-07T13:25:36Z 2015-12 2015-07 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/110515 Rwei, Alina Y.; Lee, Jung-Jae; Zhan, Changyou; Liu, Qian; Ok, Meryem T.; Shankarappa, Sahadev A.; Langer, Robert and Kohane, Daniel S.“Repeatable and Adjustable on-Demand Sciatic Nerve Block with Phototriggerable Liposomes.” Proceedings of the National Academy of Sciences 112, 51 (December 2015): 15719–15724 © 2015 National Academy of Sciences https://orcid.org/0000-0001-6080-579X https://orcid.org/0000-0001-8081-5143 https://orcid.org/0000-0002-0247-2875 https://orcid.org/0000-0003-4255-0492 https://orcid.org/0000-0003-0525-9479 en_US http://dx.doi.org/10.1073/pnas.1518791112 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 Shankarappa, Sahadev A.
Rwei, Alina Y
Lee, Jung-Jae
Zhan, Changyou
Liu, Qian
Ok, Meryem T.
Langer, Robert S
Kohane, Daniel S
Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes
title Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes
title_full Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes
title_fullStr Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes
title_full_unstemmed Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes
title_short Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes
title_sort repeatable and adjustable on demand sciatic nerve block with phototriggerable liposomes
url http://hdl.handle.net/1721.1/110515
https://orcid.org/0000-0001-6080-579X
https://orcid.org/0000-0001-8081-5143
https://orcid.org/0000-0002-0247-2875
https://orcid.org/0000-0003-4255-0492
https://orcid.org/0000-0003-0525-9479
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