title: β-casein nanovehicles for oral delivery of chemotherapeutic Drug combinations overcoming P-glycoprotein-mediated multidrug resistance in human gastric cancer cells.
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) 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.
authors.affiliation: Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa 3200000, Israel.|The 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.|The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion - Israel Institute of Technology, Haifa 3200000, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Bar-Zeev
authors.affiliation: The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion - Israel Institute of Technology, Haifa 3200000, Israel.
authors.forename: Yehuda G
authors.initials: YG
authors.lastname: Assaraf
authors.affiliation: Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa 3200000, Israel.|The 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.
authors.forename: Yoav D
authors.initials: YD
authors.lastname: Livney
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000284:Administration, Oral; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004359:Drug Therapy, Combination; D006801:Humans; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000737:chemistry*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; C495270:CTNNB1 protein, human; D004337:Drug Carriers; D008823:Micelles; D011804:Quinolines; D051176:beta Catenin; C402343:tariquidar; D017239:Paclitaxel
keywords: gastric cancer; multidrug resistance reversal; paclitaxel-tariquidar combination; target-activated oral delivery; β-casein micelles