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Colonic absorption of salmon calcitonin using tetradecyl maltoside (TDM) as a permeation enhancer.
MedLine Citation:
PMID:  23354154     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Calcitonin is used as a second line treatment of postmenopausal osteoporosis, but widespread acceptance is somewhat limited by subcutaneous and intranasal routes of delivery. This study attempted to enable intestinal sCT absorption in rats using the mild surfactant, tetradecyl maltoside (TDM) as an intestinal permeation enhancer. Human Caco-2 and HT29-MTX-E12 mucus-covered intestinal epithelial monolayers were used for permeation studies. Rat in situ intestinal instillation studies were conducted to evaluate the absorption of sCT with and without 0.1% w/v TDM in jejunum, ileum and colon. TDM significantly enhanced sCT permeation across intestinal epithelial monolayers, most likely due to combined paracellular and transcellular actions. In situ, TDM caused an increased absolute bioavailability of sCT in rat colon from 1.0% to 4.6%, whereas no enhancement increase was observed in ileal and jejunal instillations. Histological analysis suggested mild perturbation of colonic epithelia in segments instilled with sCT and TDM. These data suggest that the membrane composition of the colon is different to the small intestine and that it is more amenable to permeation enhancement. Thus, formulations designed to release payload in the colon could be advantageous for systemic delivery of poorly permeable molecules.
Authors:
Signe Beck Petersen; Lisette Gammelgaard Nielsen; Ulrik Lytt Rahbek; Mette Guldbrandt; David J Brayden
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-23
Journal Detail:
Title:  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences     Volume:  -     ISSN:  1879-0720     ISO Abbreviation:  Eur J Pharm Sci     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9317982     Medline TA:  Eur J Pharm Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier B.V.
Affiliation:
UCD School of Veterinary Science and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland; Novo Nordisk, ADME department, Novo Nordisk park, 2860 Måløv, Denmark.
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