Clinically Translatable Formulation Strategies for Systemic Administration of Nerve-Specific Probes

Connor W. Barth, Vidhi M. Shah, Lei G. Wang, Alexander L. Antaris, Alwin Klaassen, Jonathan Sorger, Deepa A. Rao, Darcy A. Kerr, Eric R. Henderson, Adam W.G. Alani, Summer L. Gibbs

Research output: Contribution to journalArticlepeer-review

Abstract

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, is utilized for enhanced nerve identification using fluorescence guided surgery (FGS), formulated using clinical translatable strategies. Formulated LGW01-08 is examined for toxicology, pharmacokinetics, and pharmacodynamics parameters in preparation for future clinical translation. Optimal LGW01-08 imaging doses are identified in each formulation resulting in a 10x difference between the toxicity and imaging dose window. Laparoscopic swine surgery completed using the da Vinci surgical robot (Intuitive Surgical) demonstrates the efficacy of formulated LGW01-08 for enhanced nerve identification. NIR fluorescence imaging enables clear identification of nerves buried beneath ≈3 mm of tissue that are 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.

Original languageEnglish (US)
Article number2100002
JournalAdvanced Therapeutics
Volume4
Issue number7
DOIs
StatePublished - Jul 2021

Keywords

  • fluorescence-guided surgery
  • formulation
  • nerve imaging
  • pharmacology
  • toxicology

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Pharmaceutical Science
  • Genetics(clinical)
  • Biochemistry, medical
  • Pharmacology (medical)

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