title: Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes.
abstract: 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.
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Alina Y
authors.initials: AY
authors.lastname: Rwei
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Jung-Jae
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Changyou
authors.initials: C
authors.lastname: Zhan
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Meryem T
authors.initials: MT
authors.lastname: Ok
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, 682041, India;
authors.forename: Sahadev A
authors.initials: SA
authors.lastname: Shankarappa
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 rlanger@mit.edu daniel.kohane@childrens.harvard.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; rlanger@mit.edu daniel.kohane@childrens.harvard.edu.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: D000772:Anesthesia, Local / Q000379:methods*; D000818:Animals; D008027:Light; D015227:Lipid Peroxidation; D008081:Liposomes; D008297:Male; D009407:Nerve Block / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve; D013779:Tetrodotoxin / Q000008:administration & dosage
chemical_list: D008081:Liposomes; D013779:Tetrodotoxin
keywords: light; near infrared; pain; photosensitizer; site 1 sodium-channel blocker