Abstract
Indocyanine green (ICG) is the most commonly used FDA-approved agent for clinical optical imaging, administered through injections only, due to its poor membrane permeability. Although ICG has vast potential for non-invasive non-radioactive imaging in patients, the clinical applications are limited by the invasive administration and short half-life in blood circulation. To expand the clinical value of ICG, non-toxic chitosan-based ICG-loaded films were designed for sublingual administration for near-infrared (NIR) and short-wave infrared (SWIR) optical imaging. Two film formulations were developed with different ICG release rates. Mold-casted self-emulsifying films rapidly released ICG (80% in 4 h) in the form of nanosized droplets, which were mostly swallowed and produced significant contrast of upper digestive tract to enable in vivo swallowing evaluations using NIR/SWIR imaging. Regular films released ICG slowly (80% in 25 h), allowing for steady absorption of ICG to systemic circulation. Inflammation in mouse feet was detected within 30 min after sublingual administration with a 1.43-fold fluorescence increase within 1 h at the inflammation sites, comparable to a 1.76-fold increase through intravenous injection. Administering ICG using sublingual films displayed notable potential for non-invasive diagnosis and monitoring of inflammatory conditions and swallowing disorders, addressing a current need for alternatives to ICG parenteral administration.