Nasal Spray With Cell-Penetrating Peptide Delivers GLP-1 Drugs Without Injection | Research

The takeaway

A hyaluronic acid carrier modified with octaarginine cell-penetrating peptide enables nasal delivery of protein drugs regardless of their chemical properties, achieving 20% bioavailability for GLP-1 analogs.

20% bioavailability
Nasal delivery of exendin-4 using HA-octaarginine carrier, comparable to oral semaglutide's SNAC enhancer

What the researchers found

Hyaluronic acid modified with octaarginine enables nasal absorption of protein drugs with ~20% bioavailability, independent of the drug's chemical properties, matching the SNAC enhancer used in oral semaglutide.

Why it matters

Most peptide drugs require injection. A nasal delivery system achieving 20% bioavailability could transform patient experience for GLP-1 and other peptide medications.

The numbers in context

~20% BA exenatide; 5x ↑ somatropin; equivalent to SNAC for small peptides; charge-independent; 4 drugs tested (1-22 kDa)

How the study worked

Mouse nasal absorption studies comparing HA-octaarginine carrier with SNAC and unformulated protein drugs, measuring bioavailability relative to subcutaneous injection.

Who was studied

Mice (nasal pharmacokinetic studies with 4 peptide drugs)

What this study cannot tell us

Mouse study — nasal anatomy and absorption differ from humans. Long-term nasal safety not assessed. Regulatory pathway unclear.

How to read the evidence

Animal study with strong pharmacokinetic data. Promising but requires human validation.

When this study was published

Published in 2020. Alternative delivery routes for GLP-1 drugs continue to be developed.

The bigger picture

This technology could enable needle-free delivery of multiple peptide therapeutics, improving patient compliance for chronic conditions like diabetes and obesity.

Questions still open

Does this system achieve similar bioavailability in humans?
Could it deliver larger proteins like insulin or monoclonal antibodies?
What are the long-term effects of repeated nasal exposure to cell-penetrating peptides?

Common questions

Why deliver GLP-1 drugs through the nose?

GLP-1 drugs like exendin-4 and semaglutide currently require injection, which many patients dislike. The nose has thin, blood-vessel-rich tissue that can absorb drugs quickly, and this system achieves 20% bioavailability — good for a non-injection route.

What makes this nasal delivery system work?

The system uses hyaluronic acid (which sticks to nasal tissue) modified with octaarginine, a cell-penetrating peptide that helps drugs cross cell membranes. This combination keeps the drug in contact with nasal tissue and enhances absorption regardless of the drug's properties.

Read the original research

Nasal absorption enhancement of protein drugs independent to their chemical properties in the presence of hyaluronic acid modified with tetraglycine-L-octaarginine.

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 154, 186-194

View on PubMed ↗Publisher’s paper ↗

Citation

Tomono, Takumi; Yagi, Haruya; Ukawa, Masami; Ishizaki, Seiya; Miwa, Takahiro; Nonomura, Mao; Igi, Ryoji; Kumagai, Hironori; Miyata, Kohei; Tobita, Etsuo; Kobayashi, Hideo; Sakuma, Shinji. (2020). Nasal absorption enhancement of protein drugs independent to their chemical properties in the presence of hyaluronic acid modified with tetraglycine-L-octaarginine.. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 154, 186-194. https://doi.org/10.1016/j.ejpb.2020.07.003