title: The liposomal daunorubicin plus tamoxifen: improving the stability, uptake, and biodistribution of carriers.
abstract: The synergistic effects of tamoxifen on the sensitivity of MCF-7 cells to daunorubicin have been reported. Whether the effects of daunorubicin on MCF-7/adr cells can be improved by tamoxifen in liposomes and how tamoxifen changes daunorubicin's behavior in vivo remains unclear. The aim of this study was to investigate the effects of tamoxifen on the uptake and biodistribution of daunorubicin liposomes by breast-cancer-resistant MCF-7/adr cells in vitro and in vivo. The uptake of liposomes by MCF-7/adr cells in vitro studies was measured using flow cytometry and laser confocal microscopy. The biodistributions of carriers and free drugs were evaluated by DiR dye using in vivo imaging. Tamoxifen obviously enhanced the cellular uptake of liposomes by MCF-7/adr cells in time-dependent manners. According to the results from in vivo imaging analysis, the mean fluorescence intensity of DiR liposomes with tamoxifen in the tumor regions of MCF-7/adr tumor-bearing nude mice was much stronger than that of DiR liposomes alone (16,450  ±  1,331 versus 3,666  ±  321; n = 3). Pegylated liposomes elongated the existence of daunorubicin in the circulatory system and the enhanced permeability and retention effect enhanced its concentration in local tumor tissues, which may provide the precondition for tamoxifen further promoting the uptake by MCF-7/Adr cells in vivo. Using daunorubicin liposomes and tamoxifen together generates better biodistribution profiles in tumor tissue than using daunorubicin liposomes only, which contributes to improving the therapeutic effect of breast cancer treatment.
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Research and Development of Natural Products Key Laboratory of Harbin Medical University, Daqing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shao
authors.forename: Shou-li
authors.initials: SL
authors.lastname: Sun
authors.forename: Ming-hui
authors.initials: MH
authors.lastname: Li
authors.forename: Bao-xin
authors.initials: BX
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.forename: Zhi-ying
authors.initials: ZY
authors.lastname: Shen
authors.forename: Ya-chao
authors.initials: YC
authors.lastname: Ren
authors.forename: Zhong-fei
authors.initials: ZF
authors.lastname: Hao
authors.forename: Nai-dan
authors.initials: ND
authors.lastname: Chang
authors.forename: Hai-sheng
authors.initials: HS
authors.lastname: Peng
authors.forename: Bao-feng
authors.initials: BF
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003630:Daunorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D013629:Tamoxifen; D003630:Daunorubicin