title: Reversion of multidrug resistance by co-encapsulation of doxorubicin and curcumin in chitosan/poly(butyl cyanoacrylate) nanoparticles.
abstract: Co-encapsulated doxorubicin (DOX) and curcumin (CUR) in poly(butyl cyanoacrylate) nanoparticles (PBCA-NPs) were prepared with emulsion polymerization and interfacial polymerization. The mean particle size and mean zeta potential of CUR-DOX-PBCA-NPs were 133 ± 5.34 nm in diameter and +32.23 ± 4.56 mV, respectively. The entrapment efficiencies of doxorubicin and curcumin were 49.98 ± 3.32% and 94.52 ± 3.14%, respectively. Anticancer activities and reversal efficacy of the formulations and various combination approaches were assessed using 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide assay and western blotting. The results showed that the dual-agent loaded PBCA-NPs system had the similar cytotoxicity to co-administration of two single-agent loaded PBCA-NPs (DOX-PBCA-NPs+CUR-PBCA-NPs), which was slightly higher than that of the free drug combination (DOX+CUR) and one free drug/another agent loaded PBCA-NPs combination (DOX+CUR-PBCA-NPs or CUR+DOX-PBCA-NPs). The simultaneous administration of doxorubicin and curcumin achieved the highest reversal efficacy and down-regulation of P-glycoprotein in MCF-7/ADR cell lines, an MCF-7 breast carcer cell line resistant to adriamycin. Multidrug resistance can be enhanced by combination delivery of encapsulated cytotoxic drugs and reversal agents.
authors.affiliation: The National Hepatobiliary & Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Department of Pharmaceutical Sciences - Drug Development Division, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Pharmaceutical Sciences - Drug Development Division, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA.
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Mansour
authors.affiliation: The National Hepatobiliary & Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Yangde
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Cancer Biology and Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Xingming
authors.initials: X
authors.lastname: Deng
authors.affiliation: The National Hepatobiliary & Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The National Hepatobiliary & Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Wang
authors.affiliation: The National Hepatobiliary & Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Pan
authors.affiliation: The National Hepatobiliary & Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China. Electronic address: zhaojinfeng@hotmail.com.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhao
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry*; D002850:Chromatography, Gel; D003474:Curcumin / Q000494:pharmacology; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers; D004338:Drug Combinations; D004339:Drug Compounding; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004659:Enbucrilate / Q000737:chemistry*; D005260:Female; D006801:Humans; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004337:Drug Carriers; D004338:Drug Combinations; D004317:Doxorubicin; D048271:Chitosan; D004659:Enbucrilate; D003474:Curcumin