Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme

Yu-Ling Lin,1,2,* Kai-Fu Chang,3,* Xiao-Fan Huang,3 Che-Lun Hung,4 Shyh-Chang Chen,5 Wan-Ru Chao,6,7 Kuang-Wen Liao,1,8 Nu-Man Tsai3,9 1College of Biological Science and Technology, 2Center for Bioinformatics Research, National Chiao Tung University, Hsinchu, 3School of Medical Laboratory and Biotec...

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Autores principales:	Lin YL, Chang KF, Huang XF, Hung CL, Chen SC, Chao WR, Liao KW, Tsai NM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0f06249ca9a346c996f7d346ad8db2d8
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spelling	oai:doaj.org-article:0f06249ca9a346c996f7d346ad8db2d82021-12-02T06:33:29ZLiposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme1178-2013https://doaj.org/article/0f06249ca9a346c996f7d346ad8db2d82015-09-01T00:00:00Zhttps://www.dovepress.com/liposomal-n-butylidenephthalide-protects-the-drug-from-oxidation-and-e-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yu-Ling Lin,1,2,* Kai-Fu Chang,3,* Xiao-Fan Huang,3 Che-Lun Hung,4 Shyh-Chang Chen,5 Wan-Ru Chao,6,7 Kuang-Wen Liao,1,8 Nu-Man Tsai3,9 1College of Biological Science and Technology, 2Center for Bioinformatics Research, National Chiao Tung University, Hsinchu, 3School of Medical Laboratory and Biotechnology, Chung Shan Medical University, 4Department of Computer Science and Communication Engineering, Providence University, 5Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, 6Institute of Medicine, Chung Shan Medical University, 7Department of Pathology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung, 8Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, 9Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan *These authors contributed equally to this work 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.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.Keywords: n-butylidenephthalide, lipo-PEG-PEI complex, glioblastoma multiforme, antitumorLin YLChang KFHuang XFHung CLChen SCChao WRLiao KWTsai NMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6009-6020 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lin YL Chang KF Huang XF Hung CL Chen SC Chao WR Liao KW Tsai NM Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme
description	Yu-Ling Lin,1,2,* Kai-Fu Chang,3,* Xiao-Fan Huang,3 Che-Lun Hung,4 Shyh-Chang Chen,5 Wan-Ru Chao,6,7 Kuang-Wen Liao,1,8 Nu-Man Tsai3,9 1College of Biological Science and Technology, 2Center for Bioinformatics Research, National Chiao Tung University, Hsinchu, 3School of Medical Laboratory and Biotechnology, Chung Shan Medical University, 4Department of Computer Science and Communication Engineering, Providence University, 5Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, 6Institute of Medicine, Chung Shan Medical University, 7Department of Pathology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung, 8Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, 9Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan *These authors contributed equally to this work 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.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.Keywords: n-butylidenephthalide, lipo-PEG-PEI complex, glioblastoma multiforme, antitumor
format	article
author	Lin YL Chang KF Huang XF Hung CL Chen SC Chao WR Liao KW Tsai NM
author_facet	Lin YL Chang KF Huang XF Hung CL Chen SC Chao WR Liao KW Tsai NM
author_sort	Lin YL
title	Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme
title_short	Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme
title_full	Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme
title_fullStr	Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme
title_full_unstemmed	Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme
title_sort	liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/0f06249ca9a346c996f7d346ad8db2d8
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Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme

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