Safety of the Cell-Penetrating Peptide Penetratin as an Oral Absorption Enhancer

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Novel delivery technology using cell-penetrating peptides (CPPs) have recently shown their potential and are emerging as promising candidates for an oral protein and peptide delivery systems. As with for the development of any absorption enhancer that is meant to function across an epithelial layer covering a surface highly exposed to pathogens such as the intestines, concern arises about the safety of such enhancers. The purpose of this study was to investigate the effect of 7 d of consecutive oral administrations of CPPs and a typical enterotoxin, lipopolysaccharide (LPS) to mice to determine the degree, if any, of damage caused to the hepatic tissue. Following the 7-d dosing regimen, we could not detect significantly increased levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase in plasma of mice treated with CPP and LPS compared to the controls, whereas heightened levels were observed in animals receiving the bile salt. In conclusion, the repeated use of CPPs as an oral absorption enhancer for macromolecules was found to be a safe strategy.