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      Elucidation of Permeation Molecular Mechanism of New Small Intestine Permeable Peptides


      Science Impact, Ltd.

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          Ohtsuki is working to develop a new oral medicine that allows macromolecules to go from the pass through the intestinal wall and into the blood to be diffused throughout the body - just like small molecule drugs. To do this, his team searched for small intestinal permeable peptides to improve biological drug absorption in the digestive tract. Before Ohtsuki commenced on this research, the world of biopharmaceuticals only knew of cell-penetrating peptides (CPPs). CPPs are effective at facilitating the delivery of molecules with low cell membrane permeability, such as proteins and nucleic acids, through cell membranes. However, they are not effective at improving the intentional absorption of macromolecules, or their transportation from cells to blood. "With the help of a library of viruses, or phages - which served as a model of macromolecules- and Caco-2 cells - which are widely used as human small intestine models, we were able to find and test new peptides that can facilitate biological drug absorption," says Ohtsuki. As frequently happens in science, Ohtsuki and the researchers came across their miracle peptides through exploring different theories that they believe might have validity. "That is a pleasure of research," comments Ohtsuki. "The peptides were found by our team looking more deeply into difference ideas, and we have now been studying them for the last five years." By using the phages and Caco-2 cell permeability screening assays, the team identified a cyclic peptide. "After injecting phage displaying identified peptides into the intestinal tract, the phages were detected in the systematic circulation after 20 minutes," explains Ohtsuki. "It was another surprise for us that the large objects, phages, can cross the Caco-2 cells and also across in vivo intestinal epithelial cells." The team still has to conduct a clinical trial - and that is the biggest challenge. "It is necessary to show that the cyclic peptide can facilitate intestinal absorption of drugs, especially macromolecule drugs," Ohtsuki describes. As with all pharmaceutical studies, clinical trials with real humans are always the most difficult. However, moving from Caco-2 cells to human small intestinal cells is a challenge that Ohtsuki's team is planning on achieving in future studies.

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          Author and article information

          Science Impact, Ltd.
          March 22 2019
          March 22 2019
          : 2019
          : 3
          : 73-75
          © 2019

          This work is licensed under a Creative Commons Attribution 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

          Earth & Environmental sciences, Medicine, Computer science, Agriculture, Engineering


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