# Intranasal carvacrol nanoemulsion: Stroke imaging and neuroprotective study

## TL;DR

This study develops an intranasal nanoemulsion of carvacrol to deliver the drug directly to the brain for treating stroke, showing improved brain delivery and neuroprotection.

## Contribution

A novel intranasal nanoemulsion formulation of carvacrol for direct nose-to-brain delivery in cerebral ischemia treatment is developed and validated.

## Key findings

- The nanoemulsion achieved sustained drug release and enhanced nasal permeation.
- It showed significantly higher brain bioavailability compared to intravenous administration.
- SPECT imaging confirmed localized brain uptake and strong neuroprotective effects in a stroke model.

## Abstract

Cerebral ischemia causes neuronal damage due to restricted blood flow and presents significant challenges for brain-targeted drug delivery because of the blood-brain barrier. The purpose of this study is to formulate and evaluate an intranasal oil-in-water nanoemulsion of carvacrol, a neuroprotective agent, for direct nose-to-brain delivery in treating cerebral ischemia.

Nanoemulsions were developed using high-pressure homogenization and optimized by adjusting surfactant mixture ratios and homogenization cycles. Characterization included droplet size (<200 nm), polydispersity index, zeta potential, drug content, transmission electron microscopy (TEM), and drug release profiles. Intranasal suitability was assessed through in vitro, ex vivo and in vivo studies, including pharmacokinetics, single photon emission computed tomography (SPECT) imaging, and evaluation in a middle cerebral artery occlusion rat model.

The optimized nanoemulsion showed sustained release, enhanced nasal permeation, and significantly improved brain bioavailability (Cmax = 67.79 ng mL-1 intranasal vs. 49.71 ng mL-1 intravenous). Lower systemic exposure and high targeting indices (DTE: 1317 %; DTP: 92.40 %) confirmed efficient brain delivery. SPECT imaging validated localized uptake, and the ischemia model demonstrated strong neuroprotective efficacy.

Intranasal carvacrol-loaded nanoemulsion is a promising non-invasive strategy for cerebral ischemia treatment, enabling effective brain targeting and significant therapeutic benefit.