Nose-to-Brain Delivery of Indocyanine Green in Rats

Abstract

Nose-to-brain drug delivery is a promising method for the direct introduction of chemicals and structures into the brain, bypassing the systemic circulation and the blood-brain barrier. Indocyanine green (ICG) is a near-infrared-emitting dye that is minimally toxic to humans. It is widely used in photodynamic applications, particularly in angiography and for many intraoperative staining procedures. In our study, ICG was administered intranasally to rats, and its penetration into the brain was observed. ICG distribution was measured using a near-infrared excitation laser at 1, 4, and 24 hours after administration as a solution into the rat nasal cavity near the olfactory mucosa. As a result, significant staining of the olfactory bulb and brainstem – mainly in the basolateral region of the pons – was observed in all cases, with the strongest signal detected at four hours. A more rapid decline in signal intensity was observed in the brainstem compared to the olfactory bulbs. These findings suggest that ICG readily crosses the nasal mucosal barrier and reaches the olfactory bulbs and brainstem via the olfactory and trigeminal nerve pathways, respectively. Additionally, ICG appears to be a useful dye for labelling molecules and supramolecular structures in studies of nose-to-brain delivery and whole-body distribution.