Understanding Peptide Medications
Peptides are short chains of amino acids that play essential roles in biological processes. Many peptides are already used as drugs, including:
- Insulin – Regulates blood sugar levels
- Cyclosporine – Suppresses organ rejection after transplants
- Glucagon-like peptide-1 (GLP-1) – Used in diabetes treatments
Currently, more than 40 peptide-based drugs are approved, generating billions in revenue, and hundreds more are in clinical trials. However, nearly all peptide medications must be injected because the gastrointestinal (GI) tract rapidly degrades peptides, making oral administration nearly impossible.
The Challenge of Developing Oral Peptides
The stomach and intestines contain powerful enzymes that break down peptides as part of normal digestion. When peptides are taken orally, they usually degrade before they can be absorbed into the bloodstream, limiting their effectiveness as a pill-based treatment.
This challenge has led researchers to explore cyclic peptides, which are chemically modified to increase stability. These peptides have their ends joined by chemical bridges, making them less flexible and harder for enzymes to break down.
A Breakthrough: Double-Bridged Peptides
In 2018, a research team led by Christian Heinis at Ecole Polytechnique Fédérale de Lausanne (EPFL) introduced double-bridged peptides—a new class of highly stable cyclic peptides. While promising, many of these peptides still couldn’t withstand the extreme enzymatic conditions of the GI tract.
Now, Heinis's team has developed a new screening method to identify peptides that bind to disease targets while resisting degradation. Published in Nature Biomedical Engineering, this method involves three steps:
Creating billions of genetically encoded peptide sequences, which are then cyclized with two chemical bridges for increased stability.
Testing these peptides against intestinal enzymes to eliminate unstable candidates.
Fishing out peptides that bind to disease targets by exposing the remaining peptides to specific proteins linked to various diseases.
"It's a bit like searching for a needle in a haystack, and this method makes it easy," says Heinis.
Oral Peptides vs. Injectable Peptides
The development of peptides in pill form marks a major milestone in drug delivery technology, but how do oral peptides compare to injectable peptides?
| Feature | Oral Peptides | Injectable Peptides |
|---|---|---|
| Absorption Rate | Lower—some may not fully reach the bloodstream | Higher—directly enters circulation |
| Enzyme Resistance | Requires modification for stability | Not a concern |
| Convenience | Easy to take, no injections required | Requires medical supervision or self-injection |
| Effectiveness | May be reduced due to digestion | Typically higher bioavailability |
| Targeting | Useful for treating GI-related diseases directly | Effective for systemic conditions |
Key Advantages of Peptide Pills
- Non-invasive – Eliminates the need for injections
- Patient-friendly – Easier administration for chronic treatments
- Targeted action – Can treat GI diseases without entering the bloodstream
Testing Peptide Pills in Mice
As a proof of concept, the researchers tested their new enzyme-resistant peptides in mice. They administered a peptide inhibitor of thrombin (an anti-thrombosis target) in pill form. The results showed that:
- The peptide remained intact through the stomach and intestines.
- While only small amounts reached the bloodstream, most of the peptide remained stable throughout the GI tract.
This breakthrough suggests that oral peptide drugs are within reach, particularly for diseases that can be treated directly in the gut.
The Future of Oral Peptide Drugs
Heinis's team is now working on oral peptides for gastrointestinal diseases, including:
- Crohn’s disease
- Ulcerative colitis
- Bacterial infections
Their first major success involves generating enzyme-resistant peptides targeting the interleukin-23 receptor, a key factor in inflammatory bowel disease (IBD). These peptides could provide an effective, non-invasive treatment option for millions of patients currently relying on injectable biologics.
"We have already succeeded in generating enzyme-resistant peptides against the interleukin-23 receptor, an important target of these diseases," says Heinis. "This could change the landscape for patients who currently have no oral drug options."
Conclusion: Are Peptide Pills the Future of Medicine?
Peptides have long been an essential class of medications, but their reliance on injections has limited patient accessibility. Thanks to double-bridged peptides and advanced screening techniques, the development of peptides in pill form is now a reality.
While oral peptides still face challenges in absorption and stability, they offer a promising alternative for treating chronic inflammatory diseases and GI disorders. As research continues, peptide pills may soon revolutionize medicine, making treatment easier and more convenient for millions worldwide.
Key Takeaways:
- Peptides are highly effective drugs but degrade quickly in the digestive system.
- Double-bridged peptides offer increased enzyme resistance, making oral delivery possible.
- Oral vs. injectable peptides: Injectable peptides are currently more effective, but oral forms offer greater convenience.
- New peptide pills could treat Crohn’s disease, ulcerative colitis, and bacterial infections without injections.
- Future research will focus on improving absorption rates and expanding treatment applications.
With these advancements, the era of peptide pills is fast approaching, transforming how we take peptide-based medications and offering a needle-free future for patients in need.
