研究生: |
何耳申 Arsenius - Marhendian |
---|---|
論文名稱: |
利用金屬親合原理以聚乙二醇改質提昇聚乙烯亞胺載體穩定性 Improving polyethyleneimine stability as gene delivery vector by grafting polyethylene glycol using metal ion affinity principle |
指導教授: |
曾文祺
Wen-Chi Tseng |
口試委員: |
戴 龑
Yian Tai 朱義旭 Yi-Hsu Ju 曹恒光 Heng-Kwong Tsao |
學位類別: |
碩士 Master |
系所名稱: |
工程學院 - 化學工程系 Department of Chemical Engineering |
論文出版年: | 2007 |
畢業學年度: | 95 |
語文別: | 英文 |
論文頁數: | 78 |
中文關鍵詞: | 聚乙烯亞胺穩定性 、基因傳遞載體 、聚乙二醇化 、金屬離子親合力 |
外文關鍵詞: | polyethyleneimine stability, gene delivery vector, PEGylation, metal ion affinity |
相關次數: | 點閱:203 下載:3 |
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Synthesis and characterization of a gene delivery system containing polyethyleneimine and polyethylene glycol was done. The synthesis consist of modification at the a and w termines of polyethylene glycol to obtain heterobifunctional PEG bearing a tertiaty butoxy carbonyl protected hydrazide group at the a terminus and nitrilotriacetic acid at the w terminus, while modification on polyethyleneimine was done to graft histidine residues to 5% of the total primary amine present. Characterizations were done to test the ability of the synthesized product to condense plasmid DNA (in case of polyethyleneimine) and to stabilize the formed polyethyleneimine/plasmid DNA complex (in case of polyethylene glycol). Parameters on success are particle size and the amount of DNA condensed.
Analysis by NMR shows peaks in accordance with the molecular formula on both products. Characterization result shows that the modified polyethyleneimine still retain its ability to form complex with plasmid DNA. The produced particle has an average size of 170.8 ±15.49 nm, slightly bigger than that of the unmodified counterpart. The addition of modified polyethylege glycol was shown to increase the stability of the formed complex towards competitors like bovine serum albumin or heparin. The improvement was achieved only when metal ions are chelated to the nitrilotriacetic acid end located in polyethylene glycol, suggesting the interaction happened was between histidine-metal ions-nitrilotriacetic acid. Results from cell viability assay show that the modified PEI has lower cytotoxicity compared to the unmodified one. Results also shows that by adding modified PEG the cell viability would further increase, indicating less cytotoxicity.
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