Researchers from Kumamoto University, Japan have found new ‘small intestine permeable peptides’ that can facilitate digestive tract absorption of biopharmaceutical products like insulin, antibodies, and nucleic acids. Biopharmaceuticals are medium and high molecular weight molecules that are not absorbed by the small intestine and are thus currently available only as injections.
This discovery will contribute greatly to the oral formulation of such drugs and reduce the physical and mental burden of injections for patients.
Cell-penetrating peptides (CPPs) are known to facilitate the delivery of molecules with low permeability such as proteins or nucleic acids through the cell membrane. However, with respect to the permeability of biopharmaceuticals, they are not much effective in improving their intestinal absorption.
Therefore, the researchers at Kumamoto University searched for ‘small intestine permeable peptides’ using viruses called phages. They specifically gathered the phages that permeated across the Caco-2 cell layer and analyzed the phage peptides. Three new cyclic peptides were identified that facilitated the absorption of phages in Caco-2 cells and in mouse small intestines.
Since phages are larger than biopharmaceuticals, cyclic peptides that promote their absorption across the small intestine are expected to do the same for biopharmaceuticals.
“The goal of our research was to enable the oral administration of medicines with large molecular weights. These medications are not readily absorbed by the small intestine and are typically administered through injection. We have cleared this hurdle by binding new intestine-permeable cyclic peptides to biopharmaceuticals,” said Professor Sumio Ohtsuki of Kumamoto University’s Department of Pharmaceutical Microbiology.