title: Reversal of P-glycoprotein-mediated multidrug resistance by doxorubicin and quinine co-loaded liposomes in tumor cells.
abstract: Multidrug resistance (MDR) is a major obstacle to successful clinical cancer chemotherapy. Currently, there is still unsatisfactory demand for innovative strategies as well as effective and safe reversing agent to overcome MDR. In this study, we developed a novel nanoformulation, in which doxorubicin hydrochloride (DOX) and quinine hydrochloride (QN) were simultaneously loaded into liposomes by a pH-gradient method for overcoming MDR and enhancing cytotoxicity in a doxorubicin-resistant human breast cancer cell line (MCF-7/ADR). The various factors were investigated to optimize the formulation and manufacturing conditions of DOX and QN co-loaded liposomes (DQLs). The DQL showed uniform size distribution and high encapsulation efficiency (over 90%) for both the drugs. Furthermore, DQLs significantly displayed high intracellular accumulation and potential of MDR reversal capability in MCF-7/ADR cells through the cooperation of DOX with QN, in which QN played the role as a MDR reversing agent. The IC50of DQL0.5:1 with the DOX/QN/SPC weight ratio of 0.5:1:50 was 1.80 ± 0.03 μg/mL, which was 14.23 times lower than that of free DOX in MCF-7/ADR cells. And the apoptotic percentage induced by DQL0.5:1 was also increased to 62.2%. These findings suggest that DQLs have great potential for effective treatment of MDR cancer.
authors: a College of Medicine, Hangzhou Normal University , Hangzhou , China and.
authors: Qiying
authors: Q
authors: Shen
authors: b Ministry of Education (MOE) Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou , China.
authors: Liyan
authors: L
authors: Qiu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000276:immunology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy*; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D004338:Drug Combinations; D065546:Drug Liberation; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D061986:MCF-7 Cells; D010316:Particle Size; D011803:Quinine / Q000737:chemistry* / Q000494:pharmacology; D013499:Surface Properties
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004337:Drug Carriers; D004338:Drug Combinations; D008081:Liposomes; D004317:Doxorubicin; D011803:Quinine
keywords: Co-delivery; doxorubicin; liposome; multidrug resistance reversal; quinine