Over the past decade, due to their various applications, peptides have enjoyed a great upturn in the production pipeline in biotechnology and pharmaceutical companies. The peptides have shown the advantage of being more selective over the small molecule substances due to their particular functions in the body that simple chemical compounds cannot mimic. Consequently, the greater number of its interaction with the target, the peptides have shown very few off-target effects and increased potency. In addition to this, the peptides usually have low immunogenicity, lower overall systemic toxicity, and are usually well-tolerated since the body naturally produces peptides.
The administration of peptides via the oral route has become considerably more attractive with its significant improvements in the delivery methods. Better patient compliance is observed via oral administration. In addition to the medicines, Linzess (linaclotide) and Trulance (plecanatide) that have led the oral peptide delivery wave, many other peptides with the same administration route are also being developed. Molecules like Ozempic (semaglutide), previously approved as an injection for treating metabolic disease (Type II Diabetes), are now in the last phase of Clinical Testing using an Oral Route of administration. The working mechanism of these peptides is based on the interaction with the receptors present on the surface of the pancreatic beta cells to stimulate the release of insulin for diabetes. In addition to this, the pharmaceutical industry has also moved towards rare diseases. The orphan substances have also been extended to peptides that are further targeting inflammation and infectious diseases.
A large capacity of manufacturing will be required as metabolic diseases are at record levels around the world. Since the absorption rate of these molecules is very low in the small intestine, the challenge associated with the oral delivery will be the requirement of the material in large quantities as the growth of such substances is really strong.
Peptides and proteins are high molecular weight biopolymers and consist of hydrophobic and hydrophilic appendages in their structure. Because of these properties, the peptides are not easily absorbed by the intestine. In addition to this, due to the digestive roles of the duodenum and stomach, they are degraded, due to which they might not even be available for absorption by the intestine. In simple words, when ingested, peptides are recognized as food by our bodies.
Due to these barriers, the parenteral route is the most common route of administration used for the peptide medication, of which approximately 75% is given via intramuscular, intravenous, and subcutaneous injections. Although this route is appreciable, the patients’ inconsistent blood substance concentrations, frequent injections, and low acceptability make the parenteral administration a less desirable approach. To overcome this, the peptide developers are trying to approach the oral route of administration for the peptides. Most of the peptides available in the market are either given as capsules or pills, thus representing the forms that most patients prefer.
Challenges and Opportunities for Oral Peptides
Numerous obstacles need to be overcome for successful delivery via the oral route. The first target that the developers should consider is selecting the appropriate peptides for the oral route of administration. After this, the first obstacle that needs to be taken care of is the sustainability of the oral formulation in a highly acidic stomach environment. The next is that the design of the formulation must promote dissolution in the small intestine’s high pH environment and protect the peptide from the protease enzyme’s degradation. After all this, the peptide must be absorbed into the comparatively impermeable epithelium of the intestine.
Even if these obstacles are removed, it will not be possible to administer the peptides via the oral route until therapeutically relevant bioavailability is achieved.
Despite the challenges, the orally administered peptide therapeutics have high potential. The biggest example is the ongoing production of the oral leuprolide tablet that is used in treating endometriosis. It is one of the most common gynecological disorders, and in the US, approximately 6 million women are affected by it. Currently, leuprolide, an effective treatment for endometriosis, is administered via the parenteral route, limiting its use because of the irreversibility of the depot injection, which sustains in the body for around 30 to 90 days, and the injection also causes inconvenience and pain.
A daily oral leuprolide tablet has proven to be an effective and friendly alternative to the monthly depot injections for the patients. The oral route has also motivated the patients to use more frequent and earlier medication.
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