Abstract | BACKGROUND: 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.
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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)
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Chemical References |
- Antineoplastic Agents
- Liposomes
- Phthalic Anhydrides
- Protective Agents
- poly(ethylene glycol)-co-poly(ethyleneimine)
- Polyethylene Glycols
- Polyethyleneimine
- butylidenephthalide
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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
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