研究生: |
楊霆礬 Ting-Fan Yang |
---|---|
論文名稱: |
具交聯結構之Pluronic®微胞做為藥物制放載體之研究 Crosslinked Pluronic Micelle as a Carrier for Drug Delivery |
指導教授: |
宋信文
Hsing-Wen Sung |
口試委員: | |
學位類別: |
碩士 Master |
系所名稱: |
工學院 - 化學工程學系 Department of Chemical Engineering |
論文出版年: | 2005 |
畢業學年度: | 93 |
語文別: | 中文 |
論文頁數: | 68 |
中文關鍵詞: | 藥物制放 、交聯結構 、穩定性 、藥物載體 |
外文關鍵詞: | drug delivery, crosslinked, pluronic, stability, drug carrier |
相關次數: | 點閱:3 下載:0 |
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Pluronic® block copolymers(Pluronic®高分子)為現行藥物制放系統中常被應用的兩性高分子,其在水溶液中可自行排列形成微胞。許多研究以此微胞做為藥物載體來包覆疏水性抗癌藥物,發現其具有抑制癌細胞產生抗藥性的特性。然而當Pluronic®高分子微胞進入人體內的環境,經血液或體液大量稀釋微胞的濃度後,在低於臨界微胞濃度的環境下其結構會開始瓦解,不再能夠有效地保護所包覆藥物。本研究的目的為發展一微胞殼層交聯技術,解決Pluronic®高分子微胞在環境稀釋下產生瓦解的情形。
實驗以Pluronic® block copolymer L121(L121)為材料,分為三部分來進行。第一部分實驗主要的目的為製備具交聯結構的L121微胞,實驗裡以氧化劑pyridinium chlorochromate(PCC)將L121末端的羥基(-OH)轉換成醛基(-CHO),並利用precipitation/solvent evaporation technique的技術將L121製備成微胞,再以具胺基(-NH2)的化學試劑與其殼層的醛基(-CHO)進行交聯反應。實驗中探討了交聯反應的條件及製備出來的微胞粒徑分佈與表面形態。第二部分實驗探討了材料的生物相容性與交聯前後微胞的穩定性,並以抗癌藥物paclitaxel進行藥物包覆與釋放實驗。第三部分為體外細胞實驗,主要是觀察微胞被口腔上皮癌細胞胞飲的情形,並且探討了微胞包覆paclitaxel後對癌細胞生長抑制的情形。
第一部分的實驗結果顯示,以1,4-diaminobutane做為交聯架橋,且其上胺基濃度為L121上醛基濃度5倍、交聯反應時間0.5 hr、pH值4.5與室溫為最佳交聯反應條件。交聯後的L121微胞,其粒徑大小約為100 nm。第二部分細胞活性測試(MTT assay)結果顯示,交聯後的L121微胞不會影響L121原先的細胞相容性。微胞穩定性的實驗結果發現,交聯後的L121微胞其穩定性提高了約100倍。藥物釋放結果也顯示交聯後的L121微胞較其交聯前有較緩釋的效果。第三部分體外細胞胞飲實驗結果顯示,交聯後的L121微胞能夠進入癌細胞內。體外抑制癌細胞生長定性與定量的實驗結果,也顯示交聯後的L121微胞能夠控制釋放包覆其內的paclitaxel,且有效地抑制癌細胞生長。
以上的實驗結果顯示,具交聯結構的L121微胞能提升其做為藥物載體的穩定性,延長藥物在體內循環的時間,並且能夠進入癌細胞內,有效地抑制癌細胞生長。
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