β-casein nanovehicles for oral delivery of chemotherapeutic drug combinations overcoming P-glycoprotein-mediated multidrug resistance in human gastric cancer cells
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Maya Bar-Zeev1,2,3, Yehuda G. Assaraf3, Yoav D. Livney1,2
1Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa 3200000, Israel
2The Laboratory of Food Physical Chemistry and Biopolymeric Delivery Systems for Health, Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 3200000, Israel
3The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion - Israel Institute of Technology, Haifa 3200000, Israel
Yoav D. Livney, e-mail: email@example.com
Yehuda G. Assaraf, e-mail: firstname.lastname@example.org
Keywords: β-casein micelles, target-activated oral delivery, gastric cancer, multidrug resistance reversal, paclitaxel-tariquidar combination
Received: November 18, 2015 Accepted: February 21, 2016 Published: March 10, 2016
Multidrug resistance (MDR) is a primary obstacle to curative cancer therapy. We have previously demonstrated that β-casein (β-CN) micelles (β-CM) can serve as nanovehicles for oral delivery and target-activated release of hydrophobic drugs in the stomach. Herein we introduce a novel nanosystem based on β-CM, to orally deliver a synergistic combination of a chemotherapeutic drug (Paclitaxel) and a P-glycoprotein-specific transport inhibitor (Tariquidar) individually encapsulated within β-CM, for overcoming MDR in gastric cancer. Light microscopy, dynamic light scattering and zeta potential analyses revealed solubilization of these drugs by β-CN, suppressing drug crystallization. Spectrophotometry demonstrated high loading capacity and good encapsulation efficiency, whereas spectrofluorometry revealed high affinity of these drugs to β-CN. In vitro cytotoxicity assays exhibited remarkable synergistic efficacy against human MDR gastric carcinoma cells with P-glycoprotein overexpression. Oral delivery of β-CN - based nanovehicles carrying synergistic drug combinations to the stomach constitutes a novel efficacious therapeutic system that may overcome MDR in gastric cancer.
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