title: Soluplus(®) micelles as a potential drug delivery system for reversal of resistant tumor.
abstract: Inhibiting or circumventing drug resistance by using drug delivery systems (DDSs) such as micelles has attracted significant attention recently. In this present study, a polyvinyl caprolactam-polyvinyl acetate-polyethylene (Soluplus(®)) micelle was developed as the delivery system for doxorubicin (DOX) and evaluated both in vitro and in vivo. In vitro, Soluplus(®) micelles could significantly enhance the cellular accumulation of DOX in MCF-7/DOX cells, meanwhile, P-glycoprotein (P-gp)-mediated drug efflux was inhibited which was also verified in the membrane fluidity study. And MCF-7/DOX cells were found to be more susceptible to the cytotoxic effects of DOX-M. In vivo, both the P-gp inhibitors verapamil and Soluplus(®) could improve the cytotoxicity of DOX·HCl in MCF-7/DOX tumor-bearing mice, which were further certified by the effect of Soluplus(®) on P-gp inhibition. Furthermore, the excellent antitumor efficacy of DOX-M by intravenous injection was also observed, which indicated that the P-gp inhibition effect of Soluplus(®) could enhance the susceptibility of resistant tumor to DOX in vivo. In conclusion, our study suggested that Soluplus(®) micelles might be an applicable drug delivery system for enhancing the antitumor efficacy of P-gp substrates.
authors: College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310032, PR China. Electronic address: jinxiangzjut@hotmail.com.
authors: Xiang
authors: X
authors: Jin
authors: Jiangsu Center of Safety Evaluation for Drugs, School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, PR China.
authors: Bo
authors: B
authors: Zhou
authors: Jiangsu Center of Safety Evaluation for Drugs, School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, PR China.
authors: Lezhen
authors: L
authors: Xue
authors: College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310032, PR China.
authors: Weiguang
authors: W
authors: San
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008823:Micelles; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Antitumor efficacy; Doxorubicin; P-glycoprotein; Soluplus(®) micelle