| 研究生: |
謝秉軒 Hsieh, Ping-Hsuan |
|---|---|
| 論文名稱: |
以玻璃毛細管微流體裝置製備單一尺寸之包藥微球 Production of uniform-sized drug encapsulated microspheres using a simple capillary microfluidic device |
| 指導教授: |
胡晉嘉
Hu, Jin-Jia |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 生物醫學工程學系 Department of BioMedical Engineering |
| 論文出版年: | 2013 |
| 畢業學年度: | 101 |
| 語文別: | 中文 |
| 論文頁數: | 40 |
| 中文關鍵詞: | 微球 、微流體 、海藻酸鈉 、藥物釋放 |
| 外文關鍵詞: | microsphere, microfluidic, alginate, drug delivery |
| 相關次數: | 點閱:161 下載:2 |
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藥物制放系統相較傳統給藥途徑有許多具潛力的優點。目前有各種裝置用於控制藥物釋放,可降解的微球還是最常見的,本研究之重點即是微球的製備。微球目前可用很多種方法製造,例如溶液蒸發法、奈米薄膜擠壓法或是超音波震盪法,但是這些方法做出來的微球,尺寸較不一致且耗時。過去文獻中提到微球粒徑的大小與形態在藥物制放系統之中,扮演非常關鍵的角色。本研究中我們利用同軸玻璃毛細管微流體技術製備單一尺寸大小的海藻酸鈉微球;當中內管中通入海藻酸鈉溶液,而外管通入氮氣以剪應力產出微球。探討裝置的設計、氣體及液體的流率對於微球型態、微球粒徑及粒徑分布的影響,此外,並以acetaminophen作為藥物模型,研究微球在去離子水中的藥物釋放率及微球在與不同分子量之幾丁聚醣反應後藥物的釋放率。我們發現在玻璃毛細管尖端之間的距離需在250、500μm,才能產生完整圓形微球,其海伍德圓因子為1.019。微球粒徑大小會因氣體流速增加隨之減小,溶液流速則不影響粒徑大小。與幾丁聚醣反應後之微球可大幅降低藥物釋放與膨潤率,防止藥物快速大量釋放。低分子量幾丁聚醣-海藻酸鈉微球較中分子量幾丁聚醣-海藻酸鈉微球易於釋放藥物,在海藻酸鈉濃度2%下,粒徑50μm微球較粒徑150μm微球易釋放藥物,海藻酸鈉濃度1.5%下,則相反。
Controlled release drug delivery systems provide several potential advantages over traditional methods. Biodegradable microspheres represent one of the most common carriers for controlled release drug delivery. These microspheres can be fabricated by various methods, such as the solvent evaporation, nanopore membrane extrusion, and sonication; however, these methods are generally time consuming and the resulting microspheres are generally polydispersed. Previous studies have suggested that particle size and its distribution play critical roles in drug delivery. In this study, we used a micro-capillary-based device to fabricate monodispersed microspheres and the influence of microfluidic parameters on the particle size, shape and size distributions were investigated. In addition, we further fabricated acetaminophen loaded chitosan-alginate composite microsphere and examined the cumulative release of acetaminophen in distilled water. We found that a device with tip-to-tip distance equals to 250 or 500 μm consistently produced microspheres with the Heywood circularity factor of 1.019, indicating that the microspheres were nearly spherical. The sizes of microspheres decreased with increasing gas flow rate while the flow rate of solution seemed to have little effects. Chitosan-alginate composite microspheres have significantly lower drug release rate as well as swelling ratio, indicating that controlled drug release was achieved. Also, chitosan-alginate microspheres fabricated using low molecular weight chitosan were better in drug release compared to those fabricated using medium molecular weight chitosan. Moreover, the microspheres of 50 μm diameter were better in drug release compared to microspheres of 150 μm diameter if 2% alginate was used while opposite results were observed if 1.5% alginate was used.
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