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pH-responsive polymeric micelles based on poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) for tumor-targeting and controlled delivery of doxorubicin and P-glycoprotein inhibitor

Paper ID Volume ID Publish Year Pages File Format Full-Text
328 25 2015 11 PDF Available
Title
pH-responsive polymeric micelles based on poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) for tumor-targeting and controlled delivery of doxorubicin and P-glycoprotein inhibitor
Abstract

The combination of a chemotherapeutic drug with a P-glycoprotein (P-gp) inhibitor has emerged as a promising strategy for treating multidrug resistance (MDR) cancer. To ensure that two drugs can be co-delivered to the tumor region and quickly released in tumor cells, tumor-targeted and pH-sensitive polymeric micelles were designed and prepared by combining cationic ring-opening polymerization of 2-ethyl-2-oxazoline (EOz) with anionic ring-opening polymerization of d,l-lactide (LA), and then encapsulating doxorubicin (DOX) and d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS1000) into the micelles self-assembled by poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) (PEOz-PLA) and DSPE-PEG-folate. PEOz-PLA exhibited a low critical micelle concentration and negligible cytotoxicity. The micelles enabled the rapid release of DOX when pH decreased from 7.4 to 5.0. The targeting ability of the micelles was demonstrated by in vitro flow cytometry in KBv cells and in vivo real time near-infrared fluorescence imaging in KBv tumor-bearing nude mice. The efficiency of MDR reversion for the micelles was testified by enhancement of intracellular DOX accumulation and cytotoxicity. The efficient drug delivery by the micelles was attributed to synergistic effects of folate-mediated targeting, pH-triggered drug release and TPGS1000-aroused P-gp inhibition. Therefore, the designed multifunctional polymeric micelles may have significant promise for therapeutic application of MDR cancer.

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Keywords
Poly(2-ethyl-2-oxazoline)-poly(d,l-lactide); pH-responsive polymeric micelle; Folate-targeted delivery; P-glycoprotein inhibitor; Multidrug resistance
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pH-responsive polymeric micelles based on poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) for tumor-targeting and controlled delivery of doxorubicin and P-glycoprotein inhibitor
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 17, 15 April 2015, Pages 182–192
Authors
, , , , , , , , , ,
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