| Biorelevant refinement of the Caco-2 cell culture model to assess efficacy of paracellular permeability enhancers. | |
| | |
MedLine Citation:
|
PMID: 17724658 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Epithelial cell monolayers are routinely used to evaluate efficacy of paracellular permeability enhancers (PPEs). The purpose of the present work was to investigate how biorelevant refinements to the Caco-2 cell model impact in vitro efficacy (decrease in transepithelial electrical resistance and increase in mannitol permeability) of PPEs. Standard transport buffer was replaced by fasted-state simulated intestinal fluid (FaSSIF) or serum; or stirring was performed to decrease the unstirred water layer thickness. Apical FaSSIF significantly reduced the efficacy of amphiphilic PPEs palmitoylcarnitine and hexadecylphosphocholine and reduced the amount of these PPEs associated with cells. In contrast, FaSSIF did not affect efficacy of nonamphiphilic PPEs, ethylenediaminetetraacetic acid or 3-nitrocoumarin. Basolateral serum increased the transepithelial flux of PPEs, but did not lessen their potency. Stirring increased the flux of all PPEs, and also enhanced the potency of the amphiphilic PPEs. These results show that inclusion of FaSSIF and agitation in the cellular models significantly alter the efficacy of amphiphilic PPEs but not of hydrophilic or lipophilic PPEs. Future studies should be directed at evaluating the ability to these refined in vitro systems to predict in vivo effects of PPEs. |
| | |
Authors:
|
Timothy K Tippin; Dhiren R Thakker |
Related Documents
:
|
19877368 - Revised medical criteria for evaluating malignant neoplastic diseases. final rule. 20841688 - Evaluation of a french medical multi-terminology indexer for the manual annotation of n... 7620728 - Evaluation of trainee competence. 1090968 - Radiological concepts of cholecystokinin cholecystography. 22099718 - The gastroenterologist and industry: changing winds. 19152558 - Access, sources and value of new medical information: views of final year medical stude... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Journal of pharmaceutical sciences Volume: 97 ISSN: 0022-3549 ISO Abbreviation: J Pharm Sci Publication Date: 2008 May |
Date Detail:
|
Created Date: 2008-07-23 Completed Date: 2008-08-05 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: United States |
Other Details:
|
Languages: eng Pagination: 1977-92 Citation Subset: IM |
Affiliation:
|
Division of Molecular Pharmaceutics, School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Caco-2 Cells
/
metabolism* Electric Impedance Humans Intestinal Absorption / drug effects* Palmitoylcarnitine / pharmacology Permeability Phosphorylcholine / analogs & derivatives, pharmacology |
| Chemical | |
Reg. No./Substance:
|
107-73-3/Phosphorylcholine; 1935-18-8/Palmitoylcarnitine; 58066-85-6/miltefosine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Characterization of amorphous solids with weak glass transitions using high ramp rate differential s...
Next Document: Characterization of antigens adsorbed to anionic PLG microparticles by XPS and TOF-SIMS.