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Apoptotic cascade inspired lipid nanovesicles show synergism with encapsulated paclitaxel in chemoresistant colon carcinoma

DSpace at IIT Bombay

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Title Apoptotic cascade inspired lipid nanovesicles show synergism with encapsulated paclitaxel in chemoresistant colon carcinoma
 
Creator JOSHI, N
SHANMUGAM, T
DESHMUKH, A
BANERJEE, R
 
Subject colon carcinoma
drug resistance
lipid nanovesicles
paclitaxel
phosphatidylserine
proapoptotic
P-GLYCOPROTEIN
BREAST-CANCER
DRUG-RESISTANCE
CYTOCHROME-C
IN-VIVO
CELLS
LIPOSOMES
PHOSPHATIDYLSERINE
NANOPARTICLES
PROTEIN
 
Description Inspired from the apoptotic cascade, we developed phosphatidylserine (PS)-based proapoptotic lipid nanovesicles, capable of bypassing drug resistance and exhibiting synergistic anticancer activity with encapsulated paclitaxel in chemoresistant human colon adenocarcinoma (HCT-15). Materials & methods: Nanovesicles were developed and evaluated both in vitro and in vivo for their proapoptotic activity, synergism with encapsulated paclitaxel and ability to bypass drug resistance. Results: 110 +/- 7 nm sized nanovesicles were found to be proapoptotic and synergistic with paclitaxel, and bypassed drug resistance. The formulation, with synergistic inputs from PS and paclitaxel, downregulated Ki-67 and inhibited angiogenesis leading to apoptosis by activating caspase-3 and downregulating Bcl-2, resulting in DNA fragmentation. The nanovesicles, while increasing the systemic circulation time of paclitaxel by 6.9-fold reduced systemic toxic effects of paclitaxel and were found to be nonimmunogenic. Conclusion: These results suggest the therapeutic potential of PS-based proapoptotic nanovesicles encapsulating paclitaxel in chemoresistant human colon carcinoma.
 
Publisher FUTURE MEDICINE LTD
 
Date 2014-12-28T15:03:54Z
2014-12-28T15:03:54Z
2014
 
Type Article
 
Identifier NANOMEDICINE, 9(12)1789-1805
1743-5889
1748-6963
http://dx.doi.org/10.2217/NNM.13.182
http://dspace.library.iitb.ac.in/jspui/handle/100/16824
 
Language English