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  1. NTU Theses and Dissertations Repository
  2. 生命科學院
  3. 生化科技學系
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90672
標題: 利用微流體技術開發載有紫菌素的脂質奈米載體
Development of Gentamicin-Loaded Lipid-Based Nanocarriers by Microfluidics
作者: 紀雨彤
Yu-Tung Chi
指導教授: 陳進庭
Chin-Tin Chen
關鍵字: 紫菌素,微脂體,油酸,MIC,微流體,
gentamicin,liposome,oleic acid,MIC,microfluidics,
出版年 : 2023
學位: 碩士
摘要: 紫菌素(Gentamicin)是一種廣效性的胺基醣苷類抗生素,能夠用於治療多種細菌感染,如治療外耳炎和皮膚感染。紫菌素的半衰期較短、生物利用度低,過量的紫菌素容易造成嚴重的副作用。為增加其療效,透過添加佐劑共同作用或是將紫菌素包裹在載體中,皆有利於降低紫菌素所需的劑量及可能造成的副作用。油酸(oleic acid)是一種天然存在於各種動植物脂肪和油中的脂肪酸。本研究的第一個部份透過最低抑菌濃度(minimum inhibitory concentration)及最低殺菌濃度(minimum bactericidal concentration)實驗發現紫菌素和油酸的組合能增強對革蘭式陽性菌的抑菌及殺菌能力。
奈米載體由於它的表面積比例高,能夠改變藥物的基本性質和生物活性。將紫菌素包裹在載體中有助於延長藥物釋放時間以及降低毒性來幫助紫菌素的治療。本研究第二個部份先以薄膜水合法製備包埋紫菌素的微脂體(liposome),探討不同脂質成分的微脂體對紫菌素載藥能力的差異。結果顯示使用不帶電的磷脂對紫菌素的包覆能力均低於10%,而使用帶負電的磷脂EPG為主要成分製備出的微脂體因為電性的關係,能夠有效吸引並包埋帶正電的紫菌素,使包覆效率增加至72%。但在MIC及藥物釋放實驗中發現經由薄膜水合法所製備的紫菌素微脂體(gentamicin-loaded liposome)對於細菌抑制能力及藥物釋放效率皆不佳。
為了得到有抑菌能力的脂質載體,本研究進一步利用微流道系統製備以EPG為主要脂質成分的脂質載體(LNC)。相較於gentamicin-loaded liposome,包埋在LNC的紫菌素具有較低的MIC數值。但與游離態的紫菌素相比,LNC載體中的紫菌素對於細菌的抑菌作用還是不理想。因此,為改善gentamicin-loaded LNC在藥物釋放效率及抑菌能力不佳的問題,本實驗進一步利用實驗設計(Design of Experiment)的方法進行優化,發展出具有較好抑菌效果的最佳化脂質組成配方。透過實驗設計中的混合設計模型得到最佳脂質組成比例,成功的提高了LNC的藥物釋放效率以及對細菌的抑菌能力。
Gentamicin is an aminoglycoside antibiotic which can be used to treat various bacterial infections, such as otitis externa and skin infections. However, gentamicin has short half-life and low bioavailability. The excessive use of gentamicin may lead to severe side effects, such as ototoxicity and nephrotoxicity. To increase the therapeutic efficacy, gentamicin combined with adjuvants or encapsulated in nanocarriers could be used to reduce the side effects. Oleic acid, a fatty acid present in various animal fats and plant oils, has been found to exhibit synergistic effects with gentamicin. In this study, we found that the combination of gentamicin and oleic acid could enhance the antibacterial and bactericidal activity against gram-positive bacteria through minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) test.
Nanocarriers, with their high surface area ratio, can alter the fundamental properties and bioactivity of drugs, improving pharmacokinetics and biodistribution, reducing toxicity, and the release of therapeutic agent. Gentamicin encapsulated in nanocarriers can modulate the drug release time and reduce toxicity. The second part of this study is to prepare gentamicin-loaded liposomes with different lipid compositions using the thin-film hydration method. The results showed that the encapsulation efficiency of gentamicin using non-charged phospholipids was less than 10%. Due to the electrostatic interaction, liposomes compose of negatively charged phospholipid egg phosphatidylglycerol (EPG) had an increased encapsulation efficiency of 72%. However, the prepared gentamicin-loaded liposomes exhibit poor bacterial inhibition ability and drug release efficiency.
In order to obtain lipid carriers with higher antibacterial capability, we utilized a microfluidic system to prepare lipid-based nanocarriers (LNC) containing EPG. However, the MIC values of gentamicin-loaded LNC was higher than that of free-form gentamicin. Therefore, we further employed the Design of Experiment (DoE) method to optimize the development of gentamicin-loaded LNC, aiming to increase the drug release efficiency and bactericidal activity. By using the mixture design model, the optimal lipid composition ratio was determined. The resulted gentamicin-loaded LNC has significantly enhanced the drug release efficiency and antibacterial activity against bacteria.
URI: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90672
DOI: 10.6342/NTU202302827
全文授權: 同意授權(限校園內公開)
電子全文公開日期: 2028-08-14
顯示於系所單位:生化科技學系

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