Effects of surfactant-based permeation enhancers on mannitol permeability, histology, and electrogenic ion transport responses in excised rat colonic mucosae
| Autor: | Joanne Heade, Sinead B. Bleiel, David J. Brayden, Sam Maher, Seona Waters, Fiona McCartney |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Carbachol Colon Pharmaceutical Science 02 engineering and technology In Vitro Techniques 030226 pharmacology & pharmacy Permeability Membrane Potentials Surface-Active Agents 03 medical and health sciences 0302 clinical medicine Pulmonary surfactant medicine Animals Humans Mannitol Carbon Radioisotopes Transcellular Ion transporter Diminution Ussing chamber Ion Transport Dose-Response Relationship Drug Chemistry Permeation 021001 nanoscience & nanotechnology Rats Surfactant toxicity Biophysics Intestinal permeation enhancers 0210 nano-technology Intestinal epithelial damage medicine.drug |
| Popis: | Surfactant-based intestinal permeation enhancers (PEs) are constituents of several oral macromolecule formulations in clinical trials. This study examined the interaction of a test panel of surfactant-based-PEs with isolated rat colonic mucosae mounted in Ussing chambers in an attempt to determine if increases in transepithelial permeability can be separated from induction of mucosal perturbation. The aim was to establish assess if increases in permeability (i) intestinal permeability (the apparent permeability coefficient (Papp) of [14C]-mannitol), (ii) epithelial histology, and (iii) short-circuit current (ΔIsc) responses to a cholinomimetic (carbachol, CCh). Enhancement ratio increases for Papp values followed the order: C10 > C9 = C11:1 > a bile salt blend > sodium choleate > sucrose laurate > Labrasol® >C12E8 > C12 > Cremophor® A25 > C7 > sucrose stearate > Kolliphor® HS15 > Kolliphor® TPGS. Exposures that increased the Papp by ≥2-fold over 120 min were accompanied by histological damage in 94% of tissues, and by a decreased ΔIsc response to CCh of 83%. A degree of separation between the increased Papp of [14C]-mannitol, histological damage, and diminution of the ΔIsc response to CCh was observed at selected PE concentrations (e.g. Labrasol® at 2 mg/mL). Overall, this surfactant-based PE selection caused transcellular perturbation at similar concentrations to those that enhanced permeability. European Commission - European Regional Development Fund Irish Research Council Science Foundation Ireland AnaBio Technologies Ltd |
| Databáze: | OpenAIRE |
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