臺灣博碩士論文加值系統

雙硫侖原本為治療慢性酒精上癮症，近期學者研究發現其對於卵巢癌細胞有抑制生長之效果。因此本研究乃據此開發海藻膠微米粒子，其同時搭載雙硫侖及超順磁性氧化鐵，最後評估其治療卵巢癌的潛在應用。我們使用電噴霧法透過與氯化鈣離子凝膠化製備海藻膠微米粒子及包覆藥物。通過光學顯微鏡和掃描式電子顯微鏡觀察顆粒型態，粒子的粒徑大小約為200微米，形貌為圓盤狀，成功搭載藥物達包封率98%。在細胞存活率分析顯示對於SKOV-3及CP70的細胞毒性上，雙硫侖經顆粒載體包覆可提升毒殺癌細胞之能力。於藥物濃度300微莫耳細胞存活率皆僅剩20%以下，且顆粒載體本身對於細胞並無顯著毒性。而熱治療方面當超順磁性氧化鐵濃度達到1.566毫克/毫升有較好的熱治療效果，且透過海藻膠包覆超順磁性氧化鐵可降低超順磁性氧化鐵對細胞毒性。本實驗採用雙硫崙聯合超順磁性氧化鐵進行治療。 當藥物濃度為100微莫耳並進行額外的熱治療時，細胞存活率與僅使用藥物且濃度為300微莫耳的治療結果相似，即透過熱治療的輔助可以降低藥物使用量。實驗結果顯示此海藻膠微米粒子對於治療卵巢癌是具有潛力的化熱療載體。

Disulfiram is a drug which is used to support the treatment of chronic alcoholism. Recently, it has been found to have an ability to inhibit the growth of ovarian cancer cells. Therefore, in this study, we prepared alginate microparticles loaded with disulfiram and superparamagnetic iron oxide (SPIO) which have great potential application for the treatment of ovarian cancer. The drug-encapsulating alginate microparticles are prepared under the electrospray system and then will crosslink with calcium chloride ions. The particles were observed by optical microscope (OM) and scanning electron microscope (SEM), and the particle size is about 200 μm. The morphology of microparticles is disc-shape. The drug encapsulation efficiency of microparticles reached 98%. In the cell viability assay showing that the cytotoxicity of SKOV-3 and CP70, the encapsulation of disulfiram by particles can enhance the ability to kill cancer cells. The survival rate of the drug at a concentration of 300 μM cells was only 20% or less, and the blank particles were not significantly toxic to the cells. In the heat treatment, when the SPIO concentration reaches 1.566 mg/mL, the thermal therapeutic effect is better, and the SPIO encapsulated by the alginate particles can reduce the cytotoxicity of the SPIO. This experiment uses disulfiram combined with SPIO for treatment. When the drug concentration was 100 μM and additional doing heating treatment, the cell viability was similar to that of treatment just with drug concentration of 300 μM. That is, the use of heat therapy can reduce the amount of drug used. The results of this study showed that alginate particles are potential drug carrier for the treatment of ovarian cancer.

摘要 I
ABSTRACT II
誌謝 III
目錄 IV
表目錄 VII
圖目錄 1
中英文縮寫對照表 3
第1章、緒論 4
1.1研究動機與目的 4
1.2實驗流程 5
第2章、文獻回顧 6
2.1卵巢癌 6
2.1.1卵巢癌的診斷 6
2.1.2卵巢癌的治療 7
2.2老藥新用 7
2.2.1雙硫侖(Disulfiram) 8
2.3熱治療 8
2.4藥物傳輸系統 9
2.5藥物載體材料 10
2.5.1海藻酸鈉(Alginate) 10
2.6電噴霧(Electrospray) 11

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