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Proapoptotic miltefosine nanovesicles show synergism with paclitaxel: Implications for glioblastoma multiforme therapy

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Title Proapoptotic miltefosine nanovesicles show synergism with paclitaxel: Implications for glioblastoma multiforme therapy
 
Creator THAKUR, A
JOSHI, N
SHANMUGAM, T
BANERJEE, R
 
Subject Glioblastoma multiforme
Intranasal
Blood brain barrier
Paclitaxel
Miltefosine
Lipid nanovesicles
CONVECTION-ENHANCED DELIVERY
BLOOD-BRAIN-BARRIER
P-GLYCOPROTEIN
MULTIDRUG-RESISTANCE
IN-VITRO
INTRANASAL ROUTE
TUMOR-CELLS
LIPOSOMES
MODULATION
MICE
 
Description Hexadecylphosphocholine (HePC) or miltefosine based proapoptotic lipid nanovesicles encapsulating paclitaxel for synergistic anticancer effect of paclitaxel and miltefosine in chemoresistant human glioblastoma multiforme (U-87 MG) overexpressing multidrug resistance 1 (MDR1) gene product P-glycoprotein (P-gp), were developed in this study. The nanovesicles had 100-200 nm size and a negative zeta potential (similar to-25 mV) and optimized for miltefosine content based on their physiochemical properties. With a high encapsulation efficiency of 94%, the nanovesicles showed sustained release of paclitaxel in nasal fluid and triggered release in the cerebrospinal fluid. Synergistic action of paclitaxel and miltefosine was observed with a low IC50 of 162 +/- 5 nM. The nanovesicle also overcame drug resistance and showed ATP dependent uptake via clathrin mediated pathway in glioblastoma cells. An improved therapeutic efficacy in comparison to Taxol(R), the current clinical formulation of paclitaxel was observed. Efficient brain uptake of the nanovesicles upon intranasal administration was observed in vivo and the nanovesicles were also found to be able to cross blood brain barrier. These studies therefore suggest the therapeutic potential of proapoptotic lipid nanovesicles and their feasibility for intranasal administration in the treatment of chemoresistant glioblastoma. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
 
Publisher ELSEVIER IRELAND LTD
 
Date 2014-10-14T17:07:18Z
2014-10-14T17:07:18Z
2013
 
Type Article
 
Identifier CANCER LETTERS, 334(2)274-283
http://dx.doi.org/10.1016/j.canlet.2012.08.022
http://dspace.library.iitb.ac.in/jspui/handle/100/14527
 
Language en