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.

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.

• Authors: Yu-Ling Lin, Kai-Fu Chang, Xiao-Fan Huang, Che-Lun Hung, Shyh-Chang Chen, Wan-Ru Chao, Kuang-Wen Liao, Nu-Man Tsai
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 10 Pg. 6009-20 ( 2015) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 26451107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Liposomes
• Phthalic Anhydrides
• Protective Agents
• poly(ethylene glycol)-co-poly(ethyleneimine)
• Polyethylene Glycols
• Polyethyleneimine
• butylidenephthalide

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemistry)
• Blood-Brain Barrier (drug effects)
• Brain Neoplasms (drug therapy)
• Cell Line, Tumor
• Drug Delivery Systems
• Female
• Glioblastoma (drug therapy)
• Humans
• Immunohistochemistry
• Injections, Intravenous
• Liposomes (therapeutic use)
• Male
• Mice
• Mice, Nude
• Phthalic Anhydrides (administration & dosage)
• Polyethylene Glycols (chemistry)
• Polyethyleneimine (analogs & derivatives, chemistry)
• Protective Agents (therapeutic use)
• Spectrometry, Fluorescence
• Xenograft Model Antitumor Assays