title: Enhanced combination therapy effect on paclitaxel-resistant carcinoma by chloroquine co-delivery via liposomes.
abstract: A novel composite liposomal system co-encapsulating paclitaxel (PTX) with chloroquine phosphate (CQ) was designed for treating PTX-resistant carcinoma. It was confirmed that liposomal CQ can sensitize PTX by means of autophagy inhibition and competitively binding with multidrug-resistance transporters. Furthermore, according to the in vitro cytotoxicity and apoptosis assay, real-time observation of cellular uptake, and in vivo tissue distribution study, co-encapsulation of PTX and CQ in liposomes was validated as superior to the mixture of PTX liposome plus CQ liposome due to the simultaneous delivery and synergetic effect of the two drugs. Consequently, this composite liposome achieved significantly stronger anticancer efficacy in vivo than the PTX liposome plus CQ liposome mixture. This study helps to guide and enlighten ongoing and future clinical trials about the optimal administration modes for drug combination therapy.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Menghua
authors.initials: M
authors.lastname: Gao
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People's Republic of China ; Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008081:Liposomes; D051379:Mice; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; C023676:chloroquine diphosphate; D002738:Chloroquine; D017239:Paclitaxel
keywords: chloroquine; combination therapy; drug resistance; liposome; paclitaxel