Clinically translatable formulation strategies for systemic administration of nerve-specific probes.

Autor: Barth CW; Biomedical Engineering Department, Oregon Health & Science University, Portland, OR 97201., Shah VM; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University/OHSU, Portland, OR, 97201., Wang LG; Biomedical Engineering Department, Oregon Health & Science University, Portland, OR 97201., Antaris AL; Intuitive Surgical, Sunnyvale, CA 94086., Klaassen A; Intuitive Surgical, Sunnyvale, CA 94086., Sorger J; Intuitive Surgical, Sunnyvale, CA 94086., Rao DA; School of Pharmacy, Pacific University, Hillsboro, OR 97123., Kerr DA; Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756.; Geisel School of Mdicine at Dartmouth College, Hanover, NH 03755., Henderson ER; Department of Orthopaedics, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756., Alani AWG; Biomedical Engineering Department, Oregon Health & Science University, Portland, OR 97201.; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201.; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University/OHSU, Portland, OR, 97201., Gibbs SL; Biomedical Engineering Department, Oregon Health & Science University, Portland, OR 97201.; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201.
Jazyk: angličtina
Zdroj: Advanced therapeutics [Adv Ther (Weinh)] 2021 Jul; Vol. 4 (7). Date of Electronic Publication: 2021 May 13.
DOI: 10.1002/adtp.202100002
Abstrakt: Nerves are extremely difficult to identify and are often accidently damaged during surgery, leaving patients with lasting pain and numbness. Herein, a novel near-infrared (NIR) nerve-specific fluorophore, LGW01-08, was utilized for enhanced nerve identification using fluorescence guided surgery (FGS), formulated using clinical translatable strategies. Formulated LGW01-08 was examined for toxicology, pharmacokinetics (PK), and pharmacodynamics (PD) parameters in preparation for future clinical translation. Optimal LGW01-08 imaging doses were identified in each formulation resulting in a 10x difference between the toxicity to imaging dose window. Laparoscopic swine surgery completed using the da Vinci surgical robot (Intuitive Surgical) demonstrated the efficacy of formulated LGW01-08 for enhanced nerve identification. NIR fluorescence imaging enabled clear identification of nerves buried beneath ~3 mm of tissue that were unidentifiable by white light imaging. These studies provide a strong basis for future clinical translation of NIR nerve-specific fluorophores for utility during FGS to improve patient outcomes.
Competing Interests: COMPETING INTERESTS Alexander Antaris, Alwin Klaassen and Jonathan Sorger are employees of Intuitive Surgical. Lei Wang, Connor Barth and Summer Gibbs are inventors on patent application PCT/US19/43739 held by Oregon Health and Science University that cover the composition and methods of use of the nerve-specific oxazine compound (LGW01–08) discussed in this manuscript. Lei Wang, Connor Barth, Vidhi Shah, Adam Alani and Summer Gibbs are inventors on patent application PCT/US19/45347 held jointly by Oregon Health and Science University and Oregon State University that covers the compositions and methods of use of the formulation strategies developed herein. Lei Wang, Connor Barth and Summer Gibbs are co-founders of Inherent Targeting, LLC.
Databáze: MEDLINE
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