AsianScientist (Oct. 2, 2017) – Scientists in Japan have discovered small protein-based molecules that can improve the absorption of drugs in the digestive tract. Their findings, published in the Journal of Controlled Release, could help researchers replace injections with pills.
Orally administered medicines are among the most convenient and safest types of medications. Many drugs currently on the market are low molecular weight compounds that can be absorbed by the small intestine.
Bio-medicines such as insulin, antibodies and nucleic acids have attracted attention in recent years but are almost completely unabsorbed in the small intestine because they are macromolecular compounds with large constituent molecular weights. Therefore, there are currently no oral formulations for these biopharmaceuticals, so they are administered through injections, which are physically and mentally burdensome to the patient.
Although researchers have explored the use of cell-penetrating peptides to carry drugs from the gastrointestinal tract into the epithelial cells of the small intestine, transportation of the drugs from inside the cells to the blood is still not efficient.
In this study, researchers from Kumamoto University in Japan searched for small intestinal permeable peptides to improve biopharmaceuticals absorption in the digestive tract. They genetically modified viruses known as phages; each phage displayed circular peptides of varying sequence on its surface. The researchers then analyzed the phages that were able to pass through a layer of Caco-2 cells, which are widely used as a human small intestine absorption model.
Three new cyclic peptides were identified as a result of the analysis. In mouse models, these cyclic peptides facilitated the absorption of phages the small intestines. An analysis of these cyclic peptides found that they are transferred into the cell through macropinocytosis, a mechanism used by cells to uptake large, extracellular substances.
“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. “We expect that our developments will lead to improved patient quality of life.”
The article can be found at: Yamaguchi et al. (2017) Identification of Cyclic Peptides for Facilitation of Transcellular Transport of Phages Across Intestinal Epithelium in vitro and in vivo.
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Source: Kumamoto University; Photo: Shutterstock.
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