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Comparison of paclitaxel penetration in normal and cancerous cervical model monolayer membranes

DSpace at IIT Bombay

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Field Value
 
Title Comparison of paclitaxel penetration in normal and cancerous cervical model monolayer membranes
 
Creator PREETHA, A
HUILGOL, N
BANERJEE, R
 
Subject physiological models
langmuir blodgett films
drug products
tumors
 
Description The aim of the present study was to evaluate the penetration of paclitaxel in normal as well as cancerous human cervical monolayer membranes and to compare these results with the paclitaxel penetration in a model dipalmitoylphosphatidylcholine (DPPC) monolayer. At physiologically relevant surface pressures of 30 mN/m, equilibrium drug penetration was observed in DPPC model membrane, whereas in cervical lipid model membranes exclusion of the drug and destabilization of the membrane was observed. The maximum surface pressure increment due to penetration (Δπmax) of 600 nM paclitaxel, for DPPC monolayer was found to be 3.6, 5.4 and 5.0 times higher than those for penetration in the cancerous monolayer at surface pressures 10, 20 and 30 mN/m, respectively. At initial surface pressure 10 mN/m, the maximum surface pressure increment, for 600 nM paclitaxel penetration, of normal cervical lipid membrane was double that of the cancerous cervical lipid membrane. At 30 mN/m initial surface pressure the representative IC50 concentration of the drug produced negligible drug penetration and significant membrane destabilization in cervical lipid model membranes. The difference in penetration profile could be due to differences in composition of the model membranes. The cholesterol level in cancerous cervical membrane was 1.5-folds higher than that in the normal cervical membrane. Apart from PC, another constituent present in 20-32% in cancerous and normal membranes is sphingomyelin (SM). Introduction of 70% SM to the DPPC monolayer decreased the Δπmax from 4.7 to 1.1 mN/m, revealing the rigidifying effect of SM which was directly proportional to the amount of SM added. Modulation of fluidity of the membranes can alter the penetration of paclitaxel in biological membranes and hence its toxicity profile.
 
Publisher Elsevier
 
Date 2009-06-22T04:42:35Z
2011-12-08T08:13:43Z
2011-12-26T13:02:40Z
2011-12-27T05:49:19Z
2009-06-22T04:42:35Z
2011-12-08T08:13:43Z
2011-12-26T13:02:40Z
2011-12-27T05:49:19Z
2006
 
Type Article
 
Identifier Colloids and Surfaces B: Biointerfaces 53(2), 179-186
09277765
10.1016/j.colsurfb.2006.09.005
http://hdl.handle.net/10054/1558
http://dspace.library.iitb.ac.in/xmlui/handle/10054/1558
 
Language en