PEPTIDES & PROTEINS
Innovations in oral peptides
Although formidable challenges remain in the field of oral peptide therapeutics , major successes in the field have brought innovative and life-changing therapies to patients . For example , insulin , one of the best-known large molecule medications , has been studied for oral delivery for more than a century .
The first large molecule medication for oral delivery , Novo Nordisk ’ s Rybelsus for Type 2 diabetes , was approved in 2019 . Developed by coformulating semaglutide with the permeation enhancer sodium N- ( 8- [ 2- hydroxybenzoyl ] amino ) caprylate ( SNAC ), it overcame the challenges of oral delivery .
Today , several biopharmaceutical companies are focused on developing oral peptides , with therapies using various technologies , delivery mechanisms or permeation enhancers in clinical trials . The choice of enhancers is important , because they can help deliver the sizable proteins and peptides in question .
The quality and quantity of the enhancers make a difference to permeability and bioavailability . Several cutting-edge technologies , along with new enhancers , are making it possible for biopharmaceutical companies to revisit peptide and protein therapies that were suspended in the last few decades , further transforming the oral peptide landscape .
Future potential
Several strategies have been developed to improve the oral absorption of proteins and peptides ( Figure 2 ). Promising dosage forms , such as targeted-release tablets , mucoadhesive formulations , capsules and lipid-based delivery systems , offer new approaches to enhance stability and absorption
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( Figure 3 ). These formats aim to protect drug substances from the harsh GI environment and ensure their availability for therapeutic action .
To protect peptides and proteins from degradation caused by GI pH and enzymes , acids or alkaline salts can be added in a process called pH modulation . For example , in vitro studies have shown that SNAC , which is used to enable oral delivery of semaglutide , increases the local pH around the tablet .
This localised adjustment minimises enzymatic degradation and structural instability , improving the molecule ’ s bioavailability . Additional ingredients can also be used to modulate intestinal pH , further enhancing the stability and absorption of peptidebased compounds .
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Figure 2 - Strategies for improving oral absorption of proteins & peptides Source : Acta Pharmaceutica Sinica B 2021 ; 11 ( 8 ): 2416e2448
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Other strategies , including enteric coatings , can offer protection during stomach transit , but may need to be paired with additional techniques to address enzymatic degradation in the intestine . These approaches are paving the way for expanded therapeutic applications of oral peptides .
Regulatory hurdles
While the process for developing protein and peptide-based therapies differs slightly from the drug development journey in terms of process and flow , with the added complexities and challenges of permeability and bioavailability , it is similar to other molecules developed for oral delivery .
For OSD drugs , it is important to understand the protein on a molecular level , characterise the protein , and
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