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研究生: 賴懷鈞
Lai, Huai-Chun
論文名稱: 陰陽離子液胞/疏水改質聚核苷酸複合物於藥物傳輸載體的應用
Application of catanionic vesicle/hydrophobically modified polynucleotide complexes as drug delivery carriers
指導教授: 張鑑祥
Chang, Chien-Hsiang
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: 2025
畢業學年度: 113
語文別: 中文
論文頁數: 155
中文關鍵詞: 陰陽離子液胞疏水改質聚核苷酸藥物傳輸載體
外文關鍵詞: Catanionic vesicle, Hydrophobically modified polynucleotide, Drug delivery carriers
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  • 本研究以壬醛修飾的疏水改質聚核苷酸結合離子對雙親分子(ion pair amphiphile, IPA)製備的陰陽離子液胞形成複合物,並進行相轉移溫度、穩定性及釋放行為等測試,評估其作為藥物傳輸載體的應用潛力。實驗結果顯示,帶負電的疏水改質聚核苷酸能藉靜電吸引力吸附於帶正電的液胞表面形成穩定複合物。比起純液胞組別,該系統具有更低的相轉移溫度,推測與改質聚核苷酸結構中的疏水碳鏈插入液胞雙層膜結構、使膜流動性提升有關。接著評估複合物應用於人體的可能性,發現其在類生理的酸鹼環境(pH 6.8、7.4)中展現極好的穩定性,至於不同離子強度下則會因為電雙層壓縮等原因讓其產生輕微聚集的現象。最後,藥物釋放行為數據顯示,結合改質或未改質聚核苷酸的液胞複合物,表面緻密高分子吸附層提供了質傳阻力,降低藥物通過雙層膜到達外部介質的速率,因此表現出相對純液胞更緩慢的釋放行為;而液胞/疏水改質聚核苷酸複合物釋放速率又略高於未改質組別,推測與疏水改質碳鏈插入雙層膜後提升膜流動性有關。綜合研究結果,疏水改質聚核苷酸結合液胞後可同時有效調控液胞雙層膜性質與釋放行為,並且其在類生理環境下展現相對純液胞系統更佳的穩定性,顯示其良好的應用潛力。

    To address the challenges in the stability and controlled release of nanoscale drug carriers, this study investigates the potential of complexes formed by catanionic vesicles and hydrophobically modified polynucleotides (PN-R) as drug delivery systems. The negatively charged modified polynucleotides electrostatically adsorb onto positively charged vesicles, resulting in stable complex formation. Compared to the unmodified group, the vesicle/PN-R complexes exhibit a reduced phase transition temperature, likely due to the insertion of hydrophobic side chains into the bilayer, which enhances membrane fluidity. The vesicle/PN-R complexes demonstrate excellent stability under physiologically relevant pH conditions (pH 6.8 and 7.4), while slight aggregation is observed under high ionic strength (0.15 M), potentially due to electrical double layer compression. Drug release studies indicate that complexes with polymer coatings exhibit slower release profiles relative to bare vesicles, attributable to the presence of a dense polymer layer acting as a diffusion barrier. Notably, complexes with hydrophobically modified polynucleotides show a slightly faster release rate than their unmodified counterparts, which may be associated with increased bilayer fluidity. Overall, the results suggest that hydrophobically modified polynucleotides can effectively modulate bilayer properties and release behavior when incorporated into vesicle systems, while also enhancing colloidal stability under physiological conditions, underscoring their promise for drug delivery applications.

    摘要I Extended AbstractII 誌謝XIII 目錄XIV 表目錄XVII 圖目錄XIX 第一章 緒論1 1-1 前言1 1-2 研究動機與目的4 第二章 文獻回顧5 2-1 離子對雙親分子5 2-2 陰陽離子液胞7 2-2-1 液胞穩定性9 2-2-2液胞的相轉移行為11 2-2-3 類三碳鏈離子對雙親分子所形成的液胞17 2-3 聚核苷酸18 2-4 高分子與液胞的相互作用20 2-5 水溶性藥物包覆以及釋放25 第三章 實驗方法30 3-1 藥品30 3-2 實驗儀器及裝置31 3-2-1 元素分析儀31 3-2-2 超音波震盪及裝置31 3-2-3 雷射光散射法粒徑及界面電位分析儀32 3-2-4 微量分光光度計37 3-2-5 酸鹼度計38 3-2-6 核磁共振儀39 3-2-7 穿透式電子顯微鏡40 3-2-8 傅立葉轉換紅外光譜儀40 3-2-9 發光光譜儀41 3-3 實驗43 3-3-1 離子對雙親分子的製備43 3-3-2 液胞分散液的製備44 3-3-3 聚核苷酸的萃取45 3-3-4 疏水改質聚核苷酸的合成47 3-3-5 液胞/聚核苷酸複合物的製備47 3-3-6 液胞/疏水改質聚核苷酸複合物的製備48 3-3-7 液胞粒徑分布及界面電位的量測48 3-3-8 穿透式電子顯微鏡觀測49 3-3-9 螢光偏極化分析49 3-3-10 傅立葉紅外光譜分析50 3-3-11 複合物樣品的環境調整53 3-3-12 藥物包覆效率及釋放53 第四章 結果與討論56 4-1 離子對雙親分子56 4-2 類三碳鏈系統之陰陽離子液胞58 4-3 疏水改質聚核苷酸62 4-3-1 聚核苷酸純度62 4-3-2 疏水改質聚核苷酸接枝合成63 4-4 DHDA:HS系統中液胞/聚核苷酸以及液胞/疏水改質聚核苷酸複合物結合行為67 4-4-1 陰陽離子液胞/聚核苷酸複合物68 4-4-2 陰陽離子液胞/疏水改質聚核苷酸複合物70 4-5 DHDA:HS系統中液胞/聚核苷酸以及液胞/疏水改質聚核苷酸複合物雙層膜性質分析75 4-5-1 溫度影響75 4-5-2 膜流動性以及相轉移溫度分析77 4-6 DHDA:HS複合物系統對環境變化的表現行為86 4-6-1 酸鹼環境改變86 4-6-2 離子強度環境改變92 4-7 藥物包覆及藥物釋放行為100 4-7-1 DHDA:HS系統100 4-7-2 DHDA:DS系統106 第五章 結論112 第六章 參考文獻116

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