Cheek-Based Delivery Devices Could Eliminate Needles for Peptide Drugs Like Semaglutide | Research

The takeaway

Engineered buccal devices that deliver peptide drugs through the inner cheek lining offer a needle-free, food-restriction-free alternative to injections and oral formulations.

Needle-free, food-restriction-free
Unlike oral peptide formulations that require fasting, buccal devices can be used without food or drink restrictions — and unlike injections, they're painless and self-applied.

What the researchers found

Engineered buccal (inner cheek) devices can overcome the mucosal permeability barrier to deliver therapeutic peptides through the mouth lining. These devices use multiple mechanisms — physical epithelial disruption, convection-based mass transfer, and combined physicochemical strategies — to achieve fast, efficient peptide absorption. Importantly, minimally invasive devices can be self-applied by patients and maintain the mucosal barrier integrity after use. The buccal route avoids both the harsh gastrointestinal environment and liver first-pass metabolism that limit oral peptide delivery.

Why it matters

Most peptide drugs require injection, which is a major barrier to patient acceptance. Oral delivery has poor bioavailability due to digestive degradation. Buccal delivery through the inner cheek offers a 'best of both worlds' solution — needle-free, no food restrictions, avoids stomach degradation and liver metabolism. If these devices succeed clinically, they could transform how peptide drugs like semaglutide, insulin, and others are administered.

The numbers in context

Review covers physical disruption, convection-based transfer, and physicochemical strategies · buccal route avoids first-pass liver metabolism · no food/drink restrictions needed · minimally invasive self-applied devices · maintains barrier after exposure

How the study worked

This is a comprehensive review examining buccal physiology, the permeability barrier to peptide absorption, and engineered device strategies to overcome it. The review analyzes device performance, manufacturing considerations, patient acceptability, and commercial viability for clinical translation of buccal peptide delivery.

Who was studied

Review of buccal delivery technology for peptide therapeutics (no patient population)

What this study cannot tell us

As a review, no new experimental data are presented. Most buccal peptide delivery devices are in preclinical or early development stages. Achieving consistent bioavailability across patients with varying mucosal conditions is a challenge. Patient comfort and long-term mucosal effects of repeated device use need assessment. Regulatory pathways for combination device-drug products are complex.

How to read the evidence

This is a comprehensive review of an emerging field, covering device design principles, preclinical evidence, and translational considerations. Most technologies discussed are in early development stages, so clinical evidence is limited.

When this study was published

Published in 2025 in Advanced Drug Delivery Reviews, this is a current and authoritative overview of the buccal peptide delivery field.

The bigger picture

The peptide drug market is projected to exceed $100 billion, with injection-based delivery remaining the dominant route. Buccal delivery devices represent one of several non-invasive delivery approaches racing to eliminate needles for peptide drugs. If successful alongside oral formulations, transdermal patches, and nasal delivery, buccal devices could help the next generation of peptide therapeutics reach patients who currently refuse or struggle with injections.

Questions still open

Which specific peptide drugs are closest to clinical testing via buccal delivery devices?
How does buccal peptide bioavailability compare to the newest oral formulation technologies?
Could buccal delivery achieve the steady-state drug levels needed for GLP-1 receptor agonists used in obesity treatment?

Common questions

How does buccal delivery work for peptide drugs?

The inner cheek lining has a rich blood supply very close to the surface, and drugs absorbed here go directly into the bloodstream — bypassing both the stomach (which would destroy peptides) and the liver (which would filter them out). Engineered devices temporarily and safely increase the cheek's permeability to allow large peptide molecules through, then the tissue returns to normal. Some devices use tiny needles, others use pressure or chemical enhancers.

Why is buccal delivery better than oral peptide pills?

Oral peptide pills face two major challenges: surviving stomach acid and digestive enzymes, and crossing the intestinal wall. Current oral semaglutide achieves only about 1% bioavailability, requiring very high doses. Buccal delivery avoids the stomach entirely and doesn't go through the liver's first-pass metabolism, potentially achieving much higher bioavailability with lower doses — and without requiring the patient to fast before and after taking the medication.

Read the original research

Devices to overcome the buccal mucosal barrier to administer therapeutic peptides.

Advanced drug delivery reviews, 220, 115572

View on PubMed ↗Publisher’s paper ↗

Citation

Malhotra, Sahil; Lijnse, Thomas; Cearbhaill, Eoin O'; Brayden, David J. (2025). Devices to overcome the buccal mucosal barrier to administer therapeutic peptides.. Advanced drug delivery reviews, 220, 115572. https://doi.org/10.1016/j.addr.2025.115572