Nasal Spray Delivery of Appetite-Stimulating Ghrelin Mimetics Reaches the Brain in Mice | Research

The takeaway

Intranasal delivery of ghrelin mimetics GHRP-6 and MK-0677 successfully activated brain hunger signaling in mice, bypassing injection.

Intranasal
Nasal delivery of ghrelin mimetics successfully engaged the brain ghrelin signaling system

What the researchers found

Intranasal GHRP-6 and MK-0677 activated hypothalamic appetite neurons (NPY/AgRP) in mice, confirming brain engagement via nasal delivery.

Why it matters

A nasal spray that stimulates appetite could help cancer patients, elderly with wasting, and others who struggle to eat — without needles.

The numbers in context

GHRP-6 at 5 mg/kg intranasal increased food intake without adverse effects. Activated NPY/AgRP neurons in arcuate nucleus. Ghrelin and MK-0677 intranasal were not effective.

How the study worked

In vivo mouse study testing intranasal delivery of ghrelin, GHRP-6, and MK-0677 with assessment of hypothalamic neuron activation.

Who was studied

Mice

What this study cannot tell us

Mouse study — nasal anatomy and drug absorption differ significantly from humans. Long-term efficacy and safety not assessed.

How to read the evidence

Preclinical proof-of-concept in mice — demonstrates feasibility of intranasal delivery but far from clinical application.

When this study was published

Published in 2025, advancing the field of non-invasive peptide delivery to the brain.

The bigger picture

Intranasal peptide delivery is an emerging frontier — if ghrelin mimetics work via nasal spray, it could transform treatment of wasting conditions.

Questions still open

Would intranasal ghrelin mimetics stimulate appetite in human cachexia patients?
How does intranasal bioavailability compare to injection for these compounds?

Common questions

Could a nasal spray help stimulate appetite?

This mouse study shows ghrelin mimetics delivered nasally activate brain hunger centers, suggesting nasal sprays could eventually treat appetite loss.

What is ghrelin?

Ghrelin is the "hunger hormone" that stimulates appetite and growth hormone release. Mimicking its effects could help patients with wasting conditions.

Read the original research

Intranasal Delivery of a Ghrelin Mimetic Engages the Brain Ghrelin Signaling System in Mice.

Endocrinology, 166(3)

View on PubMed ↗Publisher’s paper ↗

Citation

Poelman, Renée; Le May, Marie V; Schéle, Erik; Stoltenborg, Iris; Dickson, Suzanne L. (2025). Intranasal Delivery of a Ghrelin Mimetic Engages the Brain Ghrelin Signaling System in Mice.. Endocrinology, 166(3). https://doi.org/10.1210/endocr/bqae166