title: Drug resistance reversal activity of anticancer drug loaded solid lipid nanoparticles in multi-drug resistant cancer cells.
abstract: The aim of our study was to enhance the cytotoxicity of anticancer drugs by reversing the resistance of multi-drug resistant cancer cells. The cytotoxicities of paclitaxel (PTX) and doxorubicin (DOX), either as single agents or loaded in solid lipid nanoparticles (SLN) by a solvent diffusion method, were examined using drug sensitive cancer cells and drug resistant cells by measuring the drug concentration required for 50% growth inhibition (IC50). Compared to Taxol and DOX·HCl solution, both PTX and DOX loaded in SLN exhibited higher cytotoxicities in human breast tumor drug sensitive MCF-7 and drug resistant MCF-7/ADR cells. The ability of PTX loaded SLN and DOX loaded SLN to reverse the drug resistance of MCF-7 cells compared to MCF-7/ADR cells was 31.0 and 4.3 fold, respectively. Both PTX and DOX loaded SLN showed the same trends of enhanced cytotoxicity against a second wild type/drug resistant human ovarian cancer cell pair SKOV3 and SKOV3-TR30 cells. The reversal powers were 3.8 and 1.9 fold for PTX loaded SLN and DOX loaded SLN, respectively.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Miao
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Du
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Xing-Guo
authors.initials: XG
authors.lastname: Zhang
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D004317:Doxorubicin; D017239:Paclitaxel