title: TPGS/Phospholipids Mixed Micelles for Delivery of Icariside II to Multidrug-Resistant Breast Cancer.
abstract: The biggest challenge for the treatment of multidrug resistant cancer is to deliver a high concentration of anticancer drugs to cancer cells. Icariside II is a flavonoid from Epimedium koreanum Nakai with remarkable anticancer properties, but poor solubility and significant efflux from cancer cells limited its clinical use. In our previous study, a self-assembled mixture of micelles (TPGS-Icariside II-phospholipid complex) was successfully constructed, which could substantially increase the solubility of Icariside II and inhibit the efflux on Caco-2 cells. In this study, we evaluate the anticancer effect of the mixed micelles encapsulating Icariside II (Icar-MC) on MCF-7/ADR, a multidrug-resistant breast cancer cell line. The cellular uptake of the micelles was confirmed by fluorescent coumarin-6-loaded micelles. The IC50 of Icar-MC in MCF-7/ADR was 2-fold less than the free drug. The in vitro study showed Icar-MC induced more apoptosis and lactate dehydrogenase release. Intravenous injection of Icar-MC into nude mice bearing MCF-7/ADR xenograft resulted in a better antitumor efficacy compared with the administration of free drug, without causing significant body weight changes in mice. The antitumor effect was further verified by magnetic resonance imaging and immunohistochemical assays for Ki-67, a proliferative indicator. Moreover, Icar-MC treatment also elevated Bax/Bcl-2 ratio and the expressions of cleaved caspase-3, -8, -9 and AIFM1 in tumors. This study suggests that phospholipid/TPGS mixed micelles might be a suitable drug delivery system for Icariside II to treat multidrug resistant breast cancer.
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China Jiangsu Provincial Academy of Chinese Medicine, Shizi Street, Jiangsu, Nanjing, China.
authors: Jie
authors: J
authors: Song
authors: Jiangsu Provincial Academy of Chinese Medicine, Shizi Street, Jiangsu, Nanjing, China.
authors: Houcai
authors: H
authors: Huang
authors: Jiangsu Provincial Academy of Chinese Medicine, Shizi Street, Jiangsu, Nanjing, China.
authors: Zhi
authors: Z
authors: Xia
authors: Jiangsu Provincial Academy of Chinese Medicine, Shizi Street, Jiangsu, Nanjing, China.
authors: Yingjie
authors: Y
authors: Wei
authors: Jiangsu Provincial Academy of Chinese Medicine, Shizi Street, Jiangsu, Nanjing, China.
authors: Nan
authors: N
authors: Yao
authors: Jiangsu Provincial Academy of Chinese Medicine, Shizi Street, Jiangsu, Nanjing, China.
authors: Li
authors: L
authors: Zhang
authors: Jiangsu Provincial Academy of Chinese Medicine, Shizi Street, Jiangsu, Nanjing, China.
authors: Hongmei
authors: H
authors: Yan
authors: Jiangsu Provincial Academy of Chinese Medicine, Shizi Street, Jiangsu, Nanjing, China jiaxiaobin2005@126.com davidpharm@yahoo.cn.
authors: Xiaobin
authors: X
authors: Jia
authors: Jiangsu Provincial Academy of Chinese Medicine, Shizi Street, Jiangsu, Nanjing, China.
authors: Zhenhai
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018938:Caco-2 Cells; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D010743:Phospholipids / Q000008:administration & dosage*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D005419:Flavonoids; D008823:Micelles; D010743:Phospholipids; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C060988:baohuoside I; D014810:Vitamin E; D020169:Caspases; C014225:tocophersolan
keywords: Icariside II; MCF-7/ADR; P-glycoprotein; micelles; multidrug resistance