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The chemotherapeutic potential of PEG-b-PLGA copolymer micelles that combine chloroquine as autophagy inhibitor and docetaxel as an anti-cancer drug

Paper ID Volume ID Publish Year Pages File Format Full-Text
5812 437 2014 11 PDF Available
Title
The chemotherapeutic potential of PEG-b-PLGA copolymer micelles that combine chloroquine as autophagy inhibitor and docetaxel as an anti-cancer drug
Abstract

Micelles may be the nanocarrier that is used most often in the area of nanomedicine due to its promising performance and technical simplicity. However, like the original drugs, micellar formulation may arouse intracellular autophagy that deteriorates their advantages for efficient drug delivery. There has been no report in the literature that involves the fate of micelles after successfully internalized into the cancer cells. In this study, we show by using docetaxel-loaded PEG-b-PLGA micelles as a micellar model that the micelles do arouse intracellular autophagy and are thus subject to degradation through the endo-lysosome pathway. Moreover, we show that co-administration of the micellar formulation with autophagy inhibitor such as chloroquine (CQ) could significantly enhance their therapeutic effects. The docetaxel-loaded PEG-b-PLGA micelles are formulated by the membrane dialysis method, which are of 7.1% drug loading and 72.8% drug encapsulation efficiency in a size range of around 40 nm with narrow size distribution. Autophagy degradation and inhibition are investigated by confocal laser scanning microscopy with various biological makers. We show that the IC50 values of the drug formulated in the PEG-b-PLGA micelles after 24 h treatment MCF-7 cancer cells with no autophagy inhibitor or in combination with CQ were 22.30 ± 1.32 and 1.75 ± 0.43 μg/mL respectively, which indicated a 12-fold more efficient treatment with CQ. The in vivo investigation further confirmed the advantages of such a strategy. The findings may provide advanced knowledge for development of nanomedicine for clinical application.

Keywords
Biodegradable polymers; Cancer nanotechnology; Chemotherapeutic engineering; Intracellular autophagy; Nanomedicine; Pharmaceutical nanotechnology
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The chemotherapeutic potential of PEG-b-PLGA copolymer micelles that combine chloroquine as autophagy inhibitor and docetaxel as an anti-cancer drug
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 33, November 2014, Pages 9144–9154
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us