title: Enhanced anticancer activity in vitro and in vivo of luteolin incorporated into long-circulating micelles based on DSPE-PEG2000 and TPGS.
abstract: OBJECTIVE
  This study aimed to evaluate enhanced anticancer activity in vitro and in vivo of luteolin-loaded long-circulating micelles (DTLLMs) formulated.
  
  
  METHODS
  DTLLM was the luteolin formulation prepared with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly (ethylene glycol 2000) (DSPE-PEG2000 ) and d-α-tocopheryl polyethylene glycol succinate (TPGS) in this study. We performed a systematic comparative evaluation of the antiproliferative effect, cellular uptake, antitumour efficacy and in vivo tumour targeting of these micelles using non-small cell lung cancer (NSCLC) A549 cells.
  
  
  RESULTS
  Results showed that the obtained micelles have a mean particle size of around 42.34 nm, and the size of micelles was narrowly distributed. With the improved cellular uptake, DTLLM displayed a more potent antiproliferative action on A549 cell lines than luteolin; half-maximal inhibitory concentration (IC50 ) was 7.29 vs 19.14 μg/ml, respectively. The antitumour efficacy test in nude mice showed that DTLLM exhibited significantly higher antitumour activity against NSCLC with lesser toxic effects on normal tissues. The imaging study for in vivo targeting demonstrated that the long-circulating micelles formulation achieved targeted drug delivery and make drug release slow to prolong the circulating time.
  
  
  CONCLUSIONS
  DTLLM might be a potential antitumour formulation.
authors.affiliation: Nanjing University of Chinese Medicine, Nanjing, China.|Third School of Clinical Medical of Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Pharmacy, Nanjing Hospital, Jiangsu Corps, The Armed Police Force, PLA, Nanjing, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Wei
authors.affiliation: Nanjing University of Chinese Medicine, Nanjing, China.|Third School of Clinical Medical of Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Song
authors.affiliation: Nanjing University of Chinese Medicine, Nanjing, China. jiaxiaobinpharmacy@163.com.|Third School of Clinical Medical of Nanjing University of Chinese Medicine, Nanjing, China. jiaxiaobinpharmacy@163.com.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Jia
authors.affiliation: Third School of Clinical Medical of Nanjing University of Chinese Medicine, Nanjing, China. davidpharm@yeah.net.
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D008175:Lung Neoplasms / Q000188:drug therapy; D047311:Luteolin / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D014810:Vitamin E / Q000737:chemistry*; D024502:alpha-Tocopherol / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D010714:Phosphatidylethanolamines; D014810:Vitamin E; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D024502:alpha-Tocopherol; D047311:Luteolin; C014225:tocophersolan
keywords: DSPE-PEG2000; TPGS; antitumour; long-circulating micelles; luteolin