Document Detail


Sparing methylation of beta-cyclodextrin mitigates cytotoxicity and permeability induction in respiratory epithelial cell layers in vitro.
MedLine Citation:
PMID:  19331849     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Cyclodextrins (CDs) are promising solubility enhancers for inhaled drug delivery. However, they have dose-dependent effects on the respiratory epithelium, which may have advantages for permeability enhancement but also gives rise to safety concerns. In this study, the methyl thiazol tetrazolium (MTT) assay was used to compare a new sparingly methylated beta-CD, Kleptose Crysmebeta (Crysmeb) with the more established CD derivatives hydroxypropyl-gamma-cyclodextrin (HPgammaCD), randomly methylated beta-cyclodextrin (Rameb) and hydroxypropyl-beta-cyclodextrin (HPbetaCD). The betaCD derivatives affected cell metabolism in A549 cells in a concentration dependent manner with LD(50) of 56, 31 and 11 mM obtained for HPbetaCD, Crysmeb and Rameb, respectively. Calu-3 cells were less susceptible to betaCD with an LD(50) of 25 mM being obtained for Rameb only. Permeability increases in Calu-3 cell layers were observed with betaCD derivatives and a concentration dependency shown. The mechanism of permeability enhancement and its reversibility was investigated. Rameb produced an irreversible loss of cell layer barrier function at > or = 25 mM, but perturbations of epithelial integrity were moderate and reversible in the case of HPbetaCD and Crysmeb (25-50 mM). Given its high solubilisation capacity, the low toxicity and transient absorption promoting properties, this study identifies Crysmeb as a promising adjuvant in formulations for inhalation.
Authors:
L Belhadj Salem; C Bosquillon; L A Dailey; L Delattre; G P Martin; B Evrard; B Forbes
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-05
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  136     ISSN:  1873-4995     ISO Abbreviation:  J Control Release     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  110-6     Citation Subset:  IM    
Affiliation:
Laboratory of Pharmaceutical Technology, University of Liège, 1 Avenue de l'Hôpital, 4000 Liège, Belgium.
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