The effect of ΔG on the transport and oral absorption of macromolecules

Delta G (ΔG) is the biologically active fragment of Zonula Occludens Toxin (Zot), an absorption enhancer, that reversibly opens the tight junctions of epithelial and endothelial cells in the small intestine and brain. This study evaluates the possible use of ΔG in enhancing the oral bioavailability...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2004-05, Vol.93 (5), p.1310-1319
Main Authors: Salama, Noha N., Fasano, Alessio, Thakar, Manjusha, Eddington, Natalie D.
Format: Article
Language:English
Subjects:
Absorption - drug effects
Absorption - physiology
absorption enhancer
Administration, Oral
Animals
bioavailability
Biological and medical sciences
Biological Transport - drug effects
Biological Transport - physiology
Caco-2 Cells
Cell Survival - drug effects
Cell Survival - physiology
Cholera Toxin - administration & dosage
Cholera Toxin - metabolism
Drug Evaluation, Preclinical - methods
General pharmacology
Humans
Macromolecular Substances - administration & dosage
Macromolecular Substances - metabolism
Male
Medical sciences
oral absorption
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Zot
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Summary:Delta G (ΔG) is the biologically active fragment of Zonula Occludens Toxin (Zot), an absorption enhancer, that reversibly opens the tight junctions of epithelial and endothelial cells in the small intestine and brain. This study evaluates the possible use of ΔG in enhancing the oral bioavailability of macromolecules using large paracellular markers as model agents. The transport of [14C]Inulin and [14C]PEG4000 was evaluated across Caco-2 cells with ΔG (0, 100, 180 μg/ml). The apparent permeability coefficients (Papp) were calculated. The in vitro toxicity of ΔG (180 μg/ml) was assessed. Sprague Dawley rats were dosed intraduodenally (ID) with the following treatments: [14C]Inulin or [14C]PEG4000 (30 μci/kg) w/o ΔG (720 μg/kg)/protease inhibitors (PI). Blood was collected and plasma was analyzed for radioactivity. ΔG (180 μg/ml) increased [14C]Inulin and [14C]PEG4000 Papp by 82.6 and 24.4%, respectively, without any toxicity. After ID administration with ΔG/PI, Cmax and AUC were significantly (p 
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.20052