研究生: |
邱奕翔 Yi-Xiang Qiu |
---|---|
論文名稱: |
以3D列印微流體裝置製備海藻酸微米顆粒並應用在改善益生菌與抗生素之傳輸 Preparation of Alginate Microbeads for Probiotic and Antibiotic Delivery via a 3D Printed Microfluidic Device |
指導教授: |
高震宇
Chen-Yu Kao |
口試委員: |
陳品銓
Pin-Chuan Chen 莊依萍 Yi-Ping Chuang |
學位類別: |
碩士 Master |
系所名稱: |
應用科技學院 - 醫學工程研究所 Graduate Institute of Biomedical Engineering |
論文出版年: | 2021 |
畢業學年度: | 109 |
語文別: | 中文 |
論文頁數: | 84 |
中文關鍵詞: | 微流道裝置 、海藻酸微米顆粒 、藥物傳輸 、微米包覆技術 、3D列印技術 |
外文關鍵詞: | microfluidic device, alginate microbeads, drug delivery, microencapsulation technology, 3D printing technology |
相關次數: | 點閱:381 下載:0 |
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透過口服藥物及益生菌來改善腸胃疾病,相較於單獨藥物的使用較為有效,然而腸胃消化道是一個複雜且多變的環境,除了蠕動、排空的現象會影響藥物作用的時間,pH值的劇烈變化以及膽鹽的濃度,也會影響益生菌的存活率。為使藥物或益生菌能夠在腸胃消化道中有更好的發揮,本研究選用海藻酸凝膠來作為包覆的材料,達到藥物傳輸及保護的用途。
海藻酸凝膠顆粒具有良好的生物相容性,且在酸性的環境下表現穩定,適合用來作為藥物載體或提供細胞及微生物保護的生醫材料。利用3D列印微流體來製備微米顆粒,相較於傳統擠壓法,此法所製備的海藻酸鈉凝膠顆粒能精準控制大小且形狀更均一,因此微流體乳化法成為製備海藻凝膠顆粒的最佳方法之一。
本研究使用3D列印技術來製作微流體,列印出具有流體聚焦結構的流道,經拋光處理後透過酒精及紫外光作用與壓克力板結合形成微流體。顆粒製備上採用微流體乳化法,先使海藻酸鈉溶液在蓖麻油中形成液滴,再利用”外部凝膠法”使液滴固化成凝膠顆粒。藉由在海藻酸鈉溶液中加入四環黴素或羅伊氏乳桿菌(Lactobacillus reuteri ),對藥物及益生菌進行包覆。並分析此方法所製備之海藻酸凝膠顆粒的大小、外觀、包埋率、藥物釋放率與益生菌存活率,藉此研究最適合在模擬腸胃道環境中釋放藥物及維持益生菌活性的海藻凝膠微粒製備條件。
我們預期此微流道平台可以製備適合藥物和益生菌遞送的海藻膠微粒,並將擴大其在藥物傳輸與食品工業的應用範圍。
Improve gastrointestinal diseases through oral drugs and probiotics, which is more effective than the use of single drugs. However, the gastrointestinal environment is complicated and varied. While Gastric motility and emptying may affect the duration of drugs, varied pH value and concentration of bile salts may decrease the viability of probiotics. To improve the efficiency of drugs and probiotics in gastrointestinal environment, alginate hydrogels were used as encapsulating material which can improve the drug delivery and provide protection.
Due to their good biocompatibility and stability under acidic environment, alginate hydrogel microbeads have become a promising biomaterial for drug delivery and cell delivery applications. Alginate hydrogel microbeads were prepared by 3D printed microfluidic device in this study. Alginate microbeads prepared via microfluidic devices exhibit more uniform in size and shapes when comparing to the traditional extrusion methods.
In this study, an inkjet 3D printer which featured rapid formation and high resolution was used to fabricate the “flow-focusing” microfluidic channels. After polishing, these channel models were bonded with PMMA sheet through ethanol and UV curing to form the microfluidic platform. A microfluidic emulsification method was used to prepare the alginate microbeads. First the alginate droplets were form in castor oil, and then were gelled to microbeads by external gelation process.
Tetracycline and Lactobacillus reuteri were encapsulated in the alginate microbeads respectively by mixing these agents in the alginate solution. The drug-loaded and probiotic-loaded microbeads were analyzed and characterized by their appearance and encapsulation efficiency. The release kinetics of the antibiotics and the viability of probiotics in the microbeads were evaluated in a simulated gastrointestinal environment.
We anticipated this novel microfluidic platform can prepare the appropriate sizes and shapes of alginate microbeads and expand their future applications in drug delivery and food industry.
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