# Intranasal Drug Delivery in Neuropharmacology: Advances in Brain-Targeted Therapies and Bioethical Challenges

## TL;DR

Intranasal drug delivery offers a direct route to the brain, bypassing the blood-brain barrier, with promising applications in treating neurological disorders and ethical challenges.

## Contribution

The paper highlights intranasal insulin's clinical efficacy in Alzheimer's and delirium, and introduces novel peptides for neuroprotection.

## Key findings

- Intranasal insulin improves cognitive scores and reduces hospital stays in Alzheimer's patients.
- Peptides like oxytocin and neuropeptide Y can be administered intranasally for neuroprotection.
- Translational gaps include anatomical differences and sex-based dosing variations in human application.

## Abstract

Intranasal drug delivery represents a transformative “backdoor” to the brain, bypassing the blood–brain barrier (BBB) that bars 98% of small molecules and nearly all large biopharmaceuticals. By harnessing the unique anatomy of the olfactory and trigeminal nerves, therapeutics can travel directly from the nasal cavity to the central nervous system, achieving therapeutic concentrations without the systemic toxicity of traditional routes. Clinical and preclinical evidence highlight the efficacy of intranasal insulin (INI) in treating Alzheimer’s disease (AD) and delirium, with studies showing significant improvements in cognitive scores and reduced hospital stays (7.9 vs. 12.9 days; p = 0.014). Additionally, other peptides can be administered intranasally like oxytocin, neuropeptide Y, and novel metabolic modulators for neuroprotection and affective disorders (AD, autism, Down syndrome). Despite these promises, critical translational gaps remain, including anatomical differences between macrosmatic rodents and microsmatic humans, and significant sex-based dosing dimorphism. The ease of intranasal administration introduces profound bioethical dilemmas regarding neuroenhancement, authenticity, and informed consent in vulnerable populations. The current literature concludes that realizing the full potential of nose-to-brain (N2B) therapy requires a commitment to precision medicine, utilizing specialized delivery devices and objective biomarkers to ensure safe and equitable clinical application.