D J Brayden1, V A Bzik, A L Lewis, L Illum. 1. School of Veterinary Medicine and Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland. david.brayden@ucd.ie
Abstract
PURPOSE: CriticalSorb™ is a novel absorption enhancer based on Solutol(®) HS15, one that has been found to enhance the nasal transport. It is in clinical trials for nasal delivery of human growth hormone. The hypothesis was that permeating enhancement effects of the Solutol(®)HS15 component would translate to the intestine. METHODS: Rat colonic mucosae were mounted in Ussing chambers and Papp values of [(14)C]-mannitol, [(14)C]-antipyrine, FITC-dextran 4000 (FD-4), and TEER values were calculated in the presence of CriticalSorb™. Tissues were fixed for H & E staining. Caco-2 monolayers were grown on Transwells™ for similar experiments. RESULTS: CriticalSorb™(0.01% v/v) significantly increased the Papp of [(14)C]-mannitol, FD-4 [(14)C]-antipyrine across ileal and colonic mucosae, accompanied by a decrease in TEER. In Caco-2 monolayers, it also increased the Papp of [(14)C]-mannitol FD-4 and [(14)C]-antipyrine over 120 min. In both monolayers and tissues, it acted as a moderately effective P-glycoprotein inhibitor. There was no evidence of cytotoxicity in Caco-2 at concentrations of 0.01% for up to 24 h and histology of tissues showed intact epithelia at 120 min. CONCLUSIONS: Solutol(®) HS15 is the key component in CriticalSorb™ that enables non-cytotoxic in vitro intestinal permeation and its mechanism of action is a combination of increased paracellular and transcellular flux.
PURPOSE: CriticalSorb™ is a novel absorption enhancer based on Solutol(®) HS15, one that has been found to enhance the nasal transport. It is in clinical trials for nasal delivery of humangrowth hormone. The hypothesis was that permeating enhancement effects of the Solutol(®)HS15 component would translate to the intestine. METHODS:Ratcolonic mucosae were mounted in Ussing chambers and Papp values of [(14)C]-mannitol, [(14)C]-antipyrine, FITC-dextran 4000 (FD-4), and TEER values were calculated in the presence of CriticalSorb™. Tissues were fixed for H & E staining. Caco-2 monolayers were grown on Transwells™ for similar experiments. RESULTS: CriticalSorb™(0.01% v/v) significantly increased the Papp of [(14)C]-mannitol, FD-4 [(14)C]-antipyrine across ileal and colonic mucosae, accompanied by a decrease in TEER. In Caco-2 monolayers, it also increased the Papp of [(14)C]-mannitol FD-4 and [(14)C]-antipyrine over 120 min. In both monolayers and tissues, it acted as a moderately effective P-glycoprotein inhibitor. There was no evidence of cytotoxicity in Caco-2 at concentrations of 0.01% for up to 24 h and histology of tissues showed intact epithelia at 120 min. CONCLUSIONS: Solutol(®) HS15 is the key component in CriticalSorb™ that enables non-cytotoxic in vitro intestinal permeation and its mechanism of action is a combination of increased paracellular and transcellular flux.
Authors: L E Buckingham; M Balasubramanian; A R Safa; H Shah; P Komarov; R M Emanuele; J S Coon Journal: Int J Cancer Date: 1996-01-03 Impact factor: 7.396
Authors: Richard G Pearson; Tahir Masud; Elaine Blackshaw; Andrew Naylor; Michael Hinchcliffe; Kirk Jeffery; Faron Jordan; Anjumn Shabir-Ahmed; Gareth King; Andrew L Lewis; Lisbeth Illum; Alan C Perkins Journal: Pharmaceutics Date: 2019-06-07 Impact factor: 6.321