標題: Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme
作者: Lin, Yu-Ling
Chang, Kai-Fu
Huang, Xiao-Fan
Hung, Che-Lun
Chen, Shyh-Chang
Chao, Wan-Ru
Liao, Kuang-Wen
Tsai, Nu-Man
生物科技學院
分子醫學與生物工程研究所
生物資訊研究中心
College of Biological Science and Technology
Institute of Molecular Medicine and Bioengineering
Center for Bioinformatics Research
關鍵字: n-butylidenephthalide;lipo-PEG-PEI complex;glioblastoma multiforme;antitumor
公開日期: 1-Jan-2015
摘要: 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 (similar to 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. Conclusion: 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.
URI: http://dx.doi.org/10.2147/IJN.S85790
http://hdl.handle.net/11536/128341
ISSN: 1178-2013
DOI: 10.2147/IJN.S85790
期刊: INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume: 10
起始頁: 6009
結束頁: 6020
Appears in Collections:Articles


Files in This Item:

  1. 51e6d36fd890c040b66e644e1954b5df.pdf