# Indocyanine Green as a Marker for Nose-to-Brain Delivery Pathways, Brain Distribution, and PLGA Nanoparticle Efficiency

## TL;DR

This study shows that indocyanine green (ICG) can be used to track brain delivery via nasal administration, with encapsulation in nanoparticles enhancing its retention.

## Contribution

The study demonstrates the long-term brain retention of ICG and its potential as a marker for nanoparticle-based brain delivery.

## Key findings

- ICG and ICG-loaded PLGA nanoparticles both stain the olfactory bulbs and brainstem after nasal administration.
- ICG encapsulated in nanoparticles shows significantly higher brain retention at 14 days compared to free ICG.
- ICG is transported into the brain via olfactory and trigeminal nerve pathways.

## Abstract

This study aims to assess the rate and duration of rat brain retention after a single intranasal administration of indocyanine green (ICG) as an aqueous solution or encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles. Near-infrared fluorescence emission of ICG from the brain and visceral organs was measured at 1, 4, and 24 h, as well as at 1 and 2 weeks after administration. It was observed that both ICG formulations stained the olfactory bulbs and brainstem, the latter mainly in the basolateral region of the pons. Reduced staining was observed on day 7 after treatment, and the signal remains detectable on day 14. Additionally, while emission from ICG-labeled brains in water decreased after two weeks compared to day 7, in ICG-loaded nanoparticles, the emission was significantly higher on day 14. It is concluded that ICG is transported into the brain via both nose-to-brain delivery pathways—through and along olfactory or trigeminal nerves—and that ICG is a useful dye for in vivo studies due to its long-lasting emission and low toxicity. Furthermore, the suggested penetration of ICG-encapsulated PLGA nanoparticles via these transport mechanisms makes them a useful carrier for brain delivery of substances that are rapidly eliminated from circulation or do not cross the blood–brain barrier.