Two separate research teams have published studies detailing novel methods for oral delivery of peptide-based drugs, which are typically administered by injection due to degradation in the stomach.
Duke University: Elastin-like Polypeptide System
Researchers at Duke University's Pratt School of Engineering developed a delivery system using elastin-like polypeptides (ELPs), naturally occurring proteins. The ELPs were engineered to change between solid and liquid states in response to stomach acidity and temperature, protecting the peptide drug as it passes through the stomach. The drug is then released for absorption in the intestines.
In tests on mice, an oral formulation of a GLP-1 receptor agonist delivered via this method resulted in weight reduction comparable to that achieved with the injected version, even when the mice had access to high-calorie food.
The research was published on May 13 in the journal Cell Biomaterials.
University of Pennsylvania: Genetically Engineered Lettuce System
A study led by researchers at the University of Pennsylvania's School of Dental Medicine investigated an oral delivery method for two GLP-1 receptor agonists, exenatide and lixisenatide. The research, published in Plant Biotechnology Journal, used genetically engineered lettuce chloroplasts to produce functional GLP-1 peptides.
The plant encapsulation protects the peptides from stomach degradation. According to the study, plant cells are resistant to human digestion, but gut bacteria break down their cell walls, releasing the peptides. The researchers stated that using natural peptide versions, as opposed to synthetic forms with artificial amino acids, may reduce the risk of gastrointestinal side effects observed with some current GLP-1 drugs.
The team is currently focused on scaling up production with plans to prepare for early-stage clinical trials.
Potential Implications
Both research teams noted that an oral version of GLP-1 drugs could make treatment more accessible.
"Approximately one in eight Americans has taken such a drug, and many patients dislike or fear injections." — Duke Team
The Penn team highlighted challenges related to manufacturing cost and delivery systems, particularly in low- and middle-income countries.
The Duke study also suggested the approach may be applicable to other peptide medicines for conditions including diabetes, digestive disorders, HIV, and osteoporosis.