Abstract
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.
References
Nov 1, 1989·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J P Nolan
Dec 27, 1995·European Journal of Pharmacology·F GantnerA Wendel
Mar 17, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·Koji NakamuraAnthony M Lowman
Jan 7, 2009·Molecular Pharmacology·Takero NakajimaToshifumi Aoyama
Jun 10, 2009·Evidence-based Complementary and Alternative Medicine : ECAM·Tomoko AkaseMasaki Aburada
Aug 4, 2009·International Journal of Pharmaceutics·El-Sayed KhafagyKozo Takayama
Oct 6, 2009·Advanced Drug Delivery Reviews·Sam MaherDavid J Brayden
Aug 25, 2011·Biomaterials·Kiran SonajeHsing-Wen Sung
Mar 6, 2012·Advanced Drug Delivery Reviews·Mariko Morishita, Nicholas A Peppas
Apr 17, 2012·International Journal of Pharmaceutics·M R Rekha, Chandra P Sharma
Jan 16, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Makoto FujimotoYutaka Shimada
Feb 23, 2013·International Journal of Pharmaceutics·Jwala RenukuntlaAshim K Mitra
Aug 22, 2013·Journal of Pharmaceutical Sciences·Noriyasu KameiMariko Takeda-Morishita
Sep 26, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·El-Sayed KhafagyMariko Takeda-Morishita
May 24, 2014·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Samir AttoubHaider Raza
Jun 29, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ebbe Juel Bech NielsenMariko Takeda-Morishita
Citations
Oct 9, 2015·Therapeutic Delivery·Jesús FominayaAngelita Rebollo
Jul 1, 2016·Tissue Barriers·Fiona McCartneyDavid J Brayden
May 8, 2016·Advanced Drug Delivery Reviews·M Sánchez-NavarroM Teixidó
Jun 21, 2016·Advanced Drug Delivery Reviews·Sam MaherDavid J Brayden
Feb 1, 2018·Nanoscale·Zhiyu HeYongming Chen
Jul 1, 2016·Tissue Barriers·Mie Kristensen, Hanne Mørck Nielsen
Jan 24, 2019·Pharmaceutics·Sam MaherLisbeth Illum
Mar 16, 2021·ACS Omega·Amine M LaradjiNathan Ravi
Jul 13, 2021·ACS Applied Bio Materials·Jessica HershSapna Deo