Abstract

An on-demand anesthetic that would only take effect when needed and where the intensity of anesthesia could be easily adjustable according to patients’ needs would be highly desirable. Here, we design and synthesize a macromolecular prodrug (P407-CM-T) in which the local anesthetic tetracaine (T) is attached to the polymer poloxamer 407 (P407) via a photo-cleavable coumarin linkage (CM). P407-CM-T solution is an injectable liquid at room temperature and gels near body temperature. The macromolecular prodrug has no anesthetic effect itself unless irradiated with a low-power blue light emitting diode (LED), resulting in local anesthesia. By adjusting the intensity and duration of irradiation, the anesthetic effect can be modulated. Local anesthesia can be repeatedly triggered.

Local anesthetic sustained release systems suffer from untriggered rapid drug release upon application. Here the authors overcome this issue by covalently linking tetracaine to a polymer gel via a photo-cleavable linkage, enabling light-triggered and repeatable drug release.

Details

Title
Light-triggered release of conventional local anesthetics from a macromolecular prodrug for on-demand local anesthesia
Author
Zhang, Wei 1   VIAFID ORCID Logo  ; Ji Tianjiao 1 ; Yang, Li 1 ; Zheng Yueqin 1 ; Mehta Manisha 1 ; Zhao, Chao 1 ; Liu, Andong 1 ; Kohane, Daniel S 1   VIAFID ORCID Logo 

1  Harvard Medical School, Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children’s Hospital, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-16177-w
ProQuest document ID
2400096958
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.