研究生: |
王鈞奕 Jyun-Yi Wang |
---|---|
論文名稱: |
一種具有標靶性化療功能的次微米藥物載體粒子製劑的開發與其在肝癌治療上的應用與改良 Development and application of micro polysaccharide drug carriers for targeting treatment of Hepatocellular Carcinoma |
指導教授: |
白孟宜
Meng-yi Bai |
口試委員: |
許維君
Wei-chun Hsu 陳榮邦 Wing-pang Chan |
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: | 2015 |
畢業學年度: | 103 |
語文別: | 中文 |
論文頁數: | 139 |
中文關鍵詞: | 幾丁聚醣 、硫酸軟骨素 、阿黴素 、藥物載體系統 、靜電噴霧技術 、次微米顆粒/粒子 、副作用 、腫瘤 |
外文關鍵詞: | Chitosan, Chondroitin sulfate, Doxorubicin, Drug delivery systems, Electrospray, Microparticles, Side effects, Tumor |
相關次數: | 點閱:444 下載:2 |
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本研究闡述如何使用硫酸軟骨素 (Chondroitin sulfate)及幾丁聚醣 (Chitosan)作為基材,透過靜電噴霧技術 (Electrospray technique)包覆化療用藥-阿黴素 (Doxorubicin),以及超順磁氧化鐵 (Superparamagnetic iron oxide),製備形成新型次微米等級之藥物載體粒子 (Drug delivery systems)之實驗方法。研究探討材料特性、體外釋放試驗、體外抗腫瘤試驗,以及活體動物模式之成效。結果顯示,此DOX-SPIO-CS/CHI 次微米粒子之平均粒徑為110.7 nm (SD = 30.23),針對Doxorubicin之包覆率約為31% (SD = 8.07),並具備緩慢釋放之特性及人類癌細胞株之體外試驗阻殺效果。在實際投藥劑量為0.06, 0.12, 0.25 nM之條件下,DOX-SPIO-CS/CHI MPs懸浮藥劑針對Hep G2之肝癌細胞存活率試驗結果分別為0.06 nM: 20.5%, 0.12 nM: 4.6%, 0.25 nM: 6.3%,DOX溶液則為0.06 nM: 70.7%, 0.12 nM: 49.9%, 0.25 nM: 21.3%;針對Huh-6之肝癌細胞存活率試驗結果分別為0.06 nM: 52.2%, 0.12 nM: 12.8%, 0.25 nM: 23.4%,DOX溶液則為0.06 nM: 71.9%, 0.12 nM: 62.5%, 0.25 nM: 43.9%。動物實驗結果顯示,針對Hep G2試驗別治療後,Exp.試驗組以68.6%之腫瘤抑制效果優於P.C.試驗組之50.8%;針對Huh-6試驗別治療後,Exp.試驗組以40%之腫瘤抑制效果優於P.C.試驗組之36.5%。此外,在兩個動物試驗別,結果皆顯示使用DOX-SPIO-CS/CHI MPs懸浮藥劑進行治療而造成較少之體重流失 (Hep G2: Exp.= -0.59%, P.C.= -5.88%; Huh-6: Exp.= +10.93%, P.C.= -0.78%)。
In this study, we describes we synthesized a novel polyelectrolyte micorparticle, DOX-SPIO-CS/CHI MPs, as drug delivery systems (DDS) for hepatic cancer treatment. Also, we investigated the properties of these micropar-ticles, from material characterizations, formulation tests, in vitro study to in vivo study. The results show that our DOX-SPIO-CS/CHI MPs displays an average diameter of 110.7 nm (SD = 30.23), and reveals a spherical shape. The encapsu-lation efficiency of doxorubicin is about 31% (SD = 8.07) based on our spec-trometer measurement. In the results of release profile test, we found a sus-tained-release behavior of DOX-SPIO-CS/CHI MPs, which released 51.5% of DOX within 48 h of testing time. Based on the results of cell viability assay and animal study, the DOX-SPIO-CS/CHI MPs was found to show stronger ability than that of free DOX, when given to Hep G2 and Huh-6 human liver cancer cell line for treatment and nude mice of Hep G2/Huh-6-induced tumor model.
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