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

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dc.contributor.author Wang, Xuexuan
dc.contributor.author Maher, Sam
dc.contributor.author Brayden, David James
dc.date.accessioned 2011-02-16T09:47:01Z
dc.date.available 2011-02-16T09:47:01Z
dc.date.copyright 2010 Future Science Ltd en
dc.date.issued 2010-07
dc.identifier.citation Therapeutic Delivery en
dc.identifier.uri http://hdl.handle.net/10197/2761
dc.description.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. en
dc.description.sponsorship Science Foundation Ireland en
dc.format.extent 296840 bytes
dc.format.mimetype application/pdf
dc.language.iso en en
dc.publisher Future Science en
dc.subject Absorption promotion en
dc.subject Rat colonic epithelium en
dc.subject Sodium caprate en
dc.subject Medium chain fatty acids en
dc.subject Oral macromolecule delivery en
dc.subject Mucosal injury en
dc.subject Epithelial repair en
dc.subject.lcsh Absorption (Physiology) en
dc.subject.lcsh Fatty acids--Physiological transport en
dc.subject.lcsh Drug carriers (Pharmacy) en
dc.subject.lcsh Fatty acids--Therapeutic use--Testing en
dc.subject.mesh Decanoic Acids--pharmacokinetics en
dc.subject.mesh Decanoic Acids--therapeutic use en
dc.subject.mesh Drug Carriers en
dc.title Restoration of rat colonic epithelium after in situ intestinal instillation of the absorption promoter, sodium caprate en
dc.type Journal Article en
dc.internal.availability Full text available en
dc.internal.webversions Publisher's version en
dc.internal.webversions http://dx.doi.org/10.4155/tde.10.5 en
dc.status Peer reviewed en
dc.identifier.volume 1 en
dc.identifier.issue 1 en
dc.identifier.startpage 75 en
dc.identifier.endpage 82 en
dc.identifier.doi 10.4155/tde.10.5
dc.neeo.contributor Wang|Xuexuan|aut| en
dc.neeo.contributor Maher|Sam|aut| en
dc.neeo.contributor Brayden|David James|aut| en
dc.description.admin Embargo until July 2011 - AV 27/01/2011 en


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