Yoav D Livney
Israel Institute of Technology, Israel
Title: β-casein nanovehicles for oral delivery of chemotherapeutic Drug combinations overcoming P-glycoprotein-mediated multidrug resistance in human gastric cancer cells
Biography
Biography: Yoav D Livney
Abstract
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, PTX) and a P-glycoprotein-specific transport inhibitor (Tariquidar TQD) 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 (4). 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.
Cytotoxicity (in terms of IC50 values) of PTX and PTX+0.8 μM TQD, with and without -CN encapsulation following simulated gastric digestion, examined using EPG85-257P, parental cell line and EPG85-257RDB multidrug resistant subline. N.S. indicates a non-significant difference, **indicates P < 0.001 and ***indicates P < 0.0001 as determined by student’s t-test.