title: Doxorubicin and chloroquine coencapsulated liposomes: preparation and improved cytotoxicity on human breast cancer cells.
abstract: Doxorubicin, as a widely used chemotherapeutic, always causes multidrug resistance in human cancer cells. To circumvent drug resistance, we developed a novel formulation where doxorubicin hydrochloride (DOX) and chloroquine phosphate (CQ) were simultaneously loaded into liposomes by a pH-gradient method where CQ played the role of a chemical sensitizer. The various factors were investigated to optimize the formulation and manufacturing conditions of DOX and CQ coencapsulated liposomes (DCL). The resultant DCLs achieved the high encapsulation efficiency of both drugs over 90%. Further, DCLs significantly displayed resistance reversal action on a doxorubicin-resistant human breast cancer cell line (MCF-7/ADR) through the cooperation of CQ with DOX. The reversal fold of DCL with the DOX/CQ/soybean phosphatidylcholine weight ratio of 0.5:1:50 was 5.7, compared to free DOX. These results demonstrate that DCL is a promising formulation for the treatment of DOX-resistant breast cancer.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. lyqiu@zju.edu.cn
authors.forename: Liyan
authors.initials: L
authors.lastname: Qiu
authors.forename: Mingfei
authors.initials: M
authors.lastname: Yao
authors.forename: Menghua
authors.initials: M
authors.lastname: Gao
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D061986:MCF-7 Cells; D008968:Molecular Conformation; D010316:Particle Size
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; C023676:chloroquine diphosphate; D004317:Doxorubicin; D002738:Chloroquine