Restoration of rat colonic epithelium after in situ intestinal instillation of the absorption promoter, sodium caprate

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Title: Restoration of rat colonic epithelium after in situ intestinal instillation of the absorption promoter, sodium caprate
Authors: Wang, Xuexuan
Maher, Sam
Brayden, David James
Permanent link: http://hdl.handle.net/10197/2761
Date: Jul-2010
Abstract: Sodium caprate (C10) is an oral absorption promoter that is currently in clinical trials as a component of solid dosage forms for poorly permeable small molecules and peptides. Clinical data with zoledronic acid tablets suggest that significant delivery along with acceptable safety can be achieved from a once-a-week dosing regime. C10 has surfactant-like properties at the high doses used in vivo and therefore we examined its effects on rat intestinal epithelium following intestinal instillation. Results: Addition of 100 mM concentrations of C10 with the paracellular flux marker, fluorescein isothiocyanate-dextran 4 kDa, permitted a bioavailability of 33% to be achieved. When C10 was added 10, 30 and 60 min in advance of fluorescein isothiocyanate-dextran 4 kDa, enhancement still occurred, but was progressively reduced. Histology revealed that the permeability increase was likely related in part to superficial epithelial damage caused in the first few minutes of exposure, which was rapidly repaired within 30–60 min. Conclusions: Design of optimized dosage forms containing C10 should co-release the payload and promoter close to the epithelium in high concentrations. While C10 induces some epithelial damage, its remarkable capacity for epithelial repair may render this effect insignificant in vivo.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: Future Science
Copyright (published version): 2010 Future Science Ltd
Keywords: Absorption promotion;Rat colonic epithelium;Sodium caprate;Medium chain fatty acids;Oral macromolecule delivery;Mucosal injury;Epithelial repair
Subject LCSH: Absorption (Physiology)
Fatty acids--Physiological transport
Drug carriers (Pharmacy)
Fatty acids--Therapeutic use--Testing
DOI: 10.4155/tde.10.5
Language: en
Status of Item: Peer reviewed
Appears in Collections:Irish Drug Delivery Network Research Collection

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