Document Detail


Cytotoxicity evaluation of enzyme inhibitors and absorption enhancers in Caco-2 cells for oral delivery of salmon calcitonin.
MedLine Citation:
PMID:  14999743     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The usefulness of enzyme inhibitors and absorption enhancers with least mucosal cell cytotoxicity was evaluated on Caco-2 cell monolayers. The temporal cytotoxicity of several protease inhibitors at 500 microg/mL (e.g., turkey and chicken ovomucoids, aprotinin, and Protease Inhibitor Cocktail) and absorption enhancers [e.g., cholate (3%), glycocholate (3%), glycosursodeoxycholate (3%), ethylenediaminetetraacetic acid (EDTA, 0.1%), hydroxypropyl-beta-cyclodextrin (HP-beta-CD, 5%), hydroxypropyl-gamma-cylcodextrin (HP-gamma-CD, 5%), gamma-cylcodextrin (gamma-CD, 5%), tetradecyl-beta-D-maltoside (0.25%), octylglucoside (0.25%), citric acid (10%), glycyrrhetinic acid (0.34 mM), and Tween-80 (0.1%)] was measured by monitoring their effect on Caco-2 cell viability. Cell viability was measured by mannitol permeability measurements, transepithelial electrical resistance (TEER) measurements, DNA-propidium iodide staining assay, and WST-1 assay (tetrazolium salt based assay). Sodium dodecyl sulfate (0.1%), a potent surfactant, was used as a positive control. Chicken and turkey ovomucoids were nontoxic to cells as evaluated by all the methods used. Aprotinin decreased the TEER, whereas plasma membrane damage was seen with Protease Inhibitor Cocktail after a 24-h period. With respect to the absorption enhancers, the toxicity increased directly as a result of an increase in the time of incubation. The enhancers EDTA and HP-beta-CD can be used safely for a short period of time, whereas glycosursodeoxycholate, glycyrrhetinic acid, octylglucoside, HP-gamma-CD, and gamma-CD can be used for a longer period.
Authors:
Rakhi B Shah; Anitha Palamakula; Mansoor A Khan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  93     ISSN:  0022-3549     ISO Abbreviation:  J Pharm Sci     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-04     Completed Date:  2004-11-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1070-82     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association.
Affiliation:
School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter, Amarillo, Texas 79106, USA.
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MeSH Terms
Descriptor/Qualifier:
Absorption / drug effects
Caco-2 Cells
Calcitonin / administration & dosage*
Cell Survival / drug effects
Coloring Agents
DNA / chemistry
Dose-Response Relationship, Drug
Electric Conductivity
Enzyme Inhibitors / toxicity*
Excipients / toxicity*
Formazans / chemistry
Humans
Mannitol / chemistry
Nuclear Envelope / drug effects
Oxidoreductases / chemistry
Propidium
Tetrazolium Salts
Thymidine / metabolism
Chemical
Reg. No./Substance:
0/2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium; 0/Coloring Agents; 0/Enzyme Inhibitors; 0/Excipients; 0/Formazans; 0/Tetrazolium Salts; 36015-30-2/Propidium; 47931-85-1/salmon calcitonin; 50-89-5/Thymidine; 69-65-8/Mannitol; 9007-12-9/Calcitonin; 9007-49-2/DNA; EC 1.-/Oxidoreductases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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