title: pH-Dependent doxorubicin release from terpolymer of starch, polymethacrylic acid and polysorbate 80 nanoparticles for overcoming multi-drug resistance in human breast cancer cells.
abstract: This work investigated the capability of a new nanoparticulate system, based on terpolymer of starch, polymethacrylic acid and polysorbate 80, to load and release doxorubicin (Dox) as a function of pH and to evaluate the anticancer activity of Dox-loaded nanoparticles (Dox-NPs) to overcome multidrug resistance (MDR) in human breast cancer cells in vitro. The Dox-NPs were characterized by Fourier transform infrared spectroscopy (FTIR), isothermal titration calorimetry (ITC), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The cellular uptake and cytotoxicity of the Dox-loaded nanoparticles were investigated using fluorescence microscopy, flow cytometry, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. The nanoparticles were able to load up to 49.7±0.3% of Dox with a high loading efficiency of 99.9±0.1%, while maintaining good colloidal stability. The nanoparticles released Dox at a higher rate at acidic pH attributable to weaker Dox-polymer molecular interactions evidenced by ITC. The Dox-NPs were taken up by the cancer cells in vitro and significantly enhanced the cytotoxicity of Dox against human MDR1 cells with up to a 20-fold decrease in the IC50 values. The results suggest that the new terpolymeric nanoparticles are a promising vehicle for the controlled delivery of Dox for treatment of drug resistant breast cancer.
authors.affiliation: Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada.
authors.forename: Alireza
authors.initials: A
authors.lastname: Shalviri
authors.forename: Gaurav
authors.initials: G
authors.lastname: Raval
authors.forename: Preethy
authors.initials: P
authors.lastname: Prasad
authors.forename: Carol
authors.initials: C
authors.lastname: Chan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Heiko
authors.initials: H
authors.lastname: Heerklotz
authors.forename: Andrew Michael
authors.initials: AM
authors.lastname: Rauth
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Wu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003102:Colloids; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004355:Drug Stability; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D053758:Nanoparticles; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D013213:Starch / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D003102:Colloids; D004337:Drug Carriers; D011108:Polymers; D011109:Polymethacrylic Acids; D011136:Polysorbates; C030613:polymethacrylic acid; D004317:Doxorubicin; D013213:Starch