Peptides are gaining recognition in health and medicine for their diverse biological roles. These molecules hold significant promise for treating various conditions, from metabolic disorders to certain cancers. The convenience of oral administration would greatly enhance patient adherence and accessibility for these promising therapeutics. This article explores the science behind whether peptides can be effectively taken by mouth.
Understanding Peptides
Peptides are short chains of amino acids, the fundamental building blocks of proteins, linked together by chemical bonds. They typically range from 2 to 50 amino acids in length, distinguishing them from larger proteins.
These chains perform a variety of functions within the body, acting as signaling molecules, hormones, and neurotransmitters. Insulin, for example, is a 51-amino-acid-long peptide hormone that facilitates the uptake of sugars into cells for energy and storage. Peptides are involved in processes like digestion, energy utilization, appetite regulation, and hormone function.
The Challenge of Oral Delivery
Delivering peptides orally presents several hurdles due to the body’s natural defenses and digestive processes. The first major obstacle is enzymatic degradation within the gastrointestinal (GI) tract. Digestive enzymes, such as pepsin in the stomach and other proteases in the intestines, are designed to break down proteins and peptides into smaller amino acids for absorption. This proteolytic activity can rapidly degrade therapeutic peptides before they can reach the bloodstream.
Beyond enzymatic breakdown, peptides face challenges in absorption due to their inherent physicochemical properties. Peptides are generally large molecules with hydrophilic (water-loving) characteristics, which makes it difficult for them to passively cross the lipophilic (fat-loving) intestinal wall and enter the bloodstream. The tight junctions between intestinal epithelial cells further restrict their passage, limiting paracellular transport.
Even if some peptides manage to survive degradation and cross the intestinal barrier, they may still be subject to first-pass metabolism in the liver. After absorption from the intestines, blood containing these compounds first travels to the liver, where enzymes can further metabolize the peptides before they reach systemic circulation, ultimately reducing their bioavailability. These combined barriers contribute to the historically low oral bioavailability of many peptide therapeutics.
Strategies for Oral Absorption
To overcome the challenges of oral peptide delivery, researchers employ various scientific and technological strategies. One approach involves chemical modifications to the peptide structure itself. Altering the amino acid sequence, cyclizing the peptide, or substituting certain amino acids can enhance resistance to enzymatic degradation and improve absorption. Other modifications can also increase stability and solubility.
Formulation strategies also play a role in protecting peptides and enhancing their absorption. Enteric coatings, for instance, are designed to shield peptides from the acidic environment of the stomach, allowing them to reach the intestine intact. Advanced delivery systems, such as nanoparticles, can encapsulate peptides, protecting them from degradation and facilitating their passage across the intestinal barrier. Permeation enhancers are another class of compounds that temporarily open the tight junctions between intestinal cells or increase membrane fluidity, allowing peptides to pass through more easily. Co-administration with protease inhibitors can also reduce enzymatic breakdown in the gut, thereby increasing the amount of intact peptide available for absorption.
Current Oral Peptide Applications
The development of successful oral peptide delivery systems has opened new avenues for therapeutic applications and nutritional supplements. A notable example in the medical field is oral semaglutide (Rybelsus®), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes. This formulation utilizes a permeation enhancer that facilitates absorption primarily in the stomach and protects the peptide from enzymatic degradation. While its bioavailability is still relatively low, its high potency and long half-life make it effective at higher doses.
Beyond prescription medications, oral peptides are commonly found in nutritional and dietary supplements. Collagen peptides, also known as hydrolyzed collagen, are a widely available example. These are smaller fragments of collagen protein that the body can more easily absorb, and they are frequently consumed in powders or pills for purported benefits related to skin health and anti-aging. Other examples include dipeptides or tripeptides, often marketed for muscle growth or other health benefits. The ongoing success of these applications underscores the convenience and improved patient compliance offered by effective oral delivery of peptides.