title: Inhibition of breast cancer with transdermal tamoxifen-encapsulated lipoplex.
abstract: BACKGROUND
  Tamoxifen is currently used for the treatment of both early and advanced estrogen receptor (ER) positive breast cancer in pre- and post-menopausal women. However, using tamoxifen routinely to inhibit endogenous or exogenous estrogen effects is occasionally difficult because of its potential side effects.
  
  
  OBJECTIVE
  The aim of this study is to design a local drug delivery system to encapsulate tamoxifen for observing their efficacy of skin penetration, drug accumulation and cancer therapy.
  
  
  METHODS
  A cationic liposome-PEG-PEI complex (LPPC) was used as a carrier for the encapsulation of tamoxifen and forming 'LPPC/TAM' for transdermal release. The cytotoxicity of LPPC/TAM was analyzed by MTT. The skin penetration, tumor growth inhibition and organ damages were measured in xenograft mice following transdermal treatment.
  
  
  RESULTS
  LPPC/TAM had an average size less than 270 nm and a zeta-potential of approximately 40 mV. LPPC/TAM displayed dramatically increased the cytotoxic activity in all breast cancer cells, especially in ER-positive breast cancer cells. In vivo, LPPC drug delivery helped the fluorescent dye penetrating across the skim and accumulating rapidly in tumor area. Administration of LPPC/TAM by transdermal route inhibited about 86 % of tumor growth in mice bearing BT474 tumors. This local treatment of LPPC/TAM did not injury skin and any organs.
  
  
  CONCLUSIONS
  LPPC-delivery system provided a better skin penetration and drug accumulation and therapeutic efficacy. Therefore, LPPC/TAM drug delivery maybe a useful transdermal tool of drugs utilization for breast cancer therapy.
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, ROC. lyring@pchome.com.tw.|Center for Bioinformatics Research, National Chiao Tung University, Hsinchu, Taiwan, ROC. lyring@pchome.com.tw.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan, ROC. swatchnctu@gmail.com.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan, ROC. variations1013@hotmail.com.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Wu
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, ROC. numan@csmu.edu.tw.|Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC. numan@csmu.edu.tw.
authors.forename: Nu-Man
authors.initials: NM
authors.lastname: Tsai
authors.affiliation: Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan, ROC. frogcty@gmail.com.
authors.forename: Ting-Yan
authors.initials: TY
authors.lastname: Jian
authors.affiliation: Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan, ROC. yuanching.chang@gmail.com.
authors.forename: Yuan-Ching
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Medical Research, MacKay Memorial Hospital, New Taipei City, Taiwan, ROC. lcs2174@gmail.com.
authors.forename: Chi-Hsin
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Surgery, En Chu Kong Hospital, New Taipei City, Taiwan, ROC. chwu@tmu.edu.tw.
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan, ROC. sakiro920@gmail.com.|Translational Imaging Research Center, Taipei Medical University, Taipei, Taiwan, ROC. sakiro920@gmail.com.
authors.forename: Fei-Ting
authors.initials: FT
authors.lastname: Hsu
authors.affiliation: Department of Diagnostic Radiology, Taipei Medical University Hospital, Taipei, Taiwan, ROC. hk8648@tmu.edu.tw.|Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan, ROC. hk8648@tmu.edu.tw.|Department of Diagnostic Radiology, Taipei Hospital, Ministry of Health and Welfare, Taipei, Taiwan, ROC. hk8648@tmu.edu.tw.|College of Science and Engineering, Fu Jen Catholic University, Hsinchuang, Taiwan, ROC. hk8648@tmu.edu.tw.
authors.forename: Ting Kai
authors.initials: TK
authors.lastname: Leung
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, ROC. lyring_tw@yahoo.com.tw.|Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan, ROC. lyring_tw@yahoo.com.tw.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC. lyring_tw@yahoo.com.tw.
authors.forename: Kuang-Wen
authors.initials: KW
authors.lastname: Liao
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001940:Breast / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage*; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000031:analogs & derivatives; D013629:Tamoxifen / Q000008:administration & dosage*
chemical_list: D008081:Liposomes; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D013629:Tamoxifen; D011092:Polyethylene Glycols; D011094:Polyethyleneimine