title: Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme.
abstract: BACKGROUND
  The natural compound n-butylidenephthalide (BP) can pass through the blood-brain barrier to inhibit the growth of glioblastoma multiforme tumors. However, BP has an unstable structure that reduces its antitumor activity and half-life in vivo.
  
  
  OBJECTIVE
  The aim of this study is to design a drug delivery system to encapsulate BP to enhance its efficacy by improving its protection and delivery.
  
  
  METHODS
  To protect its structural stability against protein-rich and peroxide solutions, BP was encapsulated into a lipo-PEG-PEI complex (LPPC). Then, the cytotoxicity of BP/LPPC following preincubation in protein-rich, acid/alkaline, and peroxide solutions was analyzed by MTT. Cell uptake of BP/LPPC was also measured by confocal microscopy. The therapeutic effects of BP/LPPC were analyzed in xenograft mice following intratumoral and intravenous injections.
  
  
  RESULTS
  When BP was encapsulated in LPPC, its cytotoxicity was maintained following preincubation in protein-rich, acid/alkaline, and peroxide solutions. The cytotoxic activity of encapsulated BP was higher than that of free BP (~4.5- to 8.5-fold). This increased cytotoxic activity of BP/LPPC is attributable to its rapid transport across the cell membrane. In an animal study, a subcutaneously xenografted glioblastoma multiforme mouse that was treated with BP by intratumoral and intravenous administration showed inhibited tumor growth. The same dose of BP/LPPC was significantly more effective in terms of tumor inhibition.
  
  
  CONCLUSIONS
  LPPC encapsulation technology is able to protect BP's structural stability and enhance its antitumor effects, thus providing a better tool for use in cancer therapy.
authors.affiliation: College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan ; Center for Bioinformatics Research, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Lin
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Kai-Fu
authors.initials: KF
authors.lastname: Chang
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Huang
authors.affiliation: Department of Computer Science and Communication Engineering, Providence University, Taichung, Taiwan.
authors.forename: Che-Lun
authors.initials: CL
authors.lastname: Hung
authors.affiliation: Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shyh-Chang
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan ; Department of Pathology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Wan-Ru
authors.initials: WR
authors.lastname: Chao
authors.affiliation: College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan ; Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Kuang-Wen
authors.initials: KW
authors.lastname: Liao
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan ; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Nu-Man
authors.initials: NM
authors.lastname: Tsai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008081:Liposomes / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010796:Phthalic Anhydrides / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry; D020011:Protective Agents / Q000627:therapeutic use; D013050:Spectrometry, Fluorescence; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D010796:Phthalic Anhydrides; D020011:Protective Agents; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D011092:Polyethylene Glycols; D011094:Polyethyleneimine; C026105:butylidenephthalide
keywords: antitumor; glioblastoma multiforme; lipo-PEG-PEI complex; n-butylidenephthalide