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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 何國川(Kuo-Chuan Ho) | |
| dc.contributor.author | Chia-Hong Su | en |
| dc.contributor.author | 蘇嘉弘 | zh_TW |
| dc.date.accessioned | 2021-06-13T00:11:45Z | - |
| dc.date.available | 2008-08-01 | |
| dc.date.copyright | 2007-08-01 | |
| dc.date.issued | 2007 | |
| dc.date.submitted | 2007-07-29 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/28548 | - |
| dc.description.abstract | 本研究主要分成四大部分，首先以共沉澱法將含有FeCl3．6H2O與
FeCl2．4H2O的前驅鹽溶液加入鹼液來共沉澱製備Fe3O4。比較由不同 鹼液所合成之Fe3O4與商用Fe3O4的粒徑分佈、表面電荷、表面型態、晶型結構與磁性質等特性分析。由實驗結果發現，以不同鹼液所合成的Fe3O4其粒徑皆大約為20nm，但由於表面電荷效應與立體障礙排斥的影響，使得粒徑分佈呈現較大的差異，其中以N(CH3)4OH為鹼液所合成的Fe3O4可得到較佳的分散懸浮效果。磁性質分析方面，透過SQUID分析，以N(CH3)4OH為鹼液所合成的Fe3O4與商用Fe3O4皆可得到約60 emu/g的飽合磁化值。根據文獻報導，飽和磁化值越大，其加熱效果越佳。 第二部分則是以氮-異丙基丙烯醯胺(N-isopropyl acrylamide, NIPAAM)與丙烯酸(Acrylic acid, AAc)、甲基丙烯酸二羥基乙酯(2-Hydroxyethyl Methacrylate, HEMA)為單體，N,N’-methylenebis acryl amide (MBA)為交聯劑，Potassium persulfate (KPS)為起始劑，以無乳化劑乳化聚合法合成溫感性微乳膠顆粒。並利用改變共聚單體之比例來調控其藥物釋放應用之標的溫度，並進行粒徑分佈、表面型態、熱性質、溫度及酸鹼感應性等性質探討。由TEM圖可觀察到粒徑約500~600 nm；而其玻璃轉移溫度則會隨著單體共聚比例而有提升或下降；低臨界溶液溫度 (Low critical solution temperature, LCST) 則隨著HEMA與AAc比例的增加而顯著的提升，並達到40℃的藥物釋放預設溫度。酸鹼感應性分析方面，HEMA系統在pH值為7，而AAc系統則在pH為9時有較佳的膨潤性。而NMR圖譜分析則可能因為交聯劑濃度高的關係導致許多特徵峰並未出現，因而無法推算共聚比例之關係。 第三部份則將上述兩部分研究結合，以化學鍵結的方式製備磁性乳膠顆粒。利用鐵氧化物於施加磁場時所產生的磁滯損耗做為溫度感應之開關，使溫感性乳膠顆粒可發生形態轉變進而釋放藥物。透過TEM以及TGA之熱分析可發現，僅AAc系統的膠體顆粒能形成較佳的包覆性，其主要之作用機制來自於COO-與Fe2+及Fe3+可形成化學鍵結使得Fe3O4可以in-situ的方式形成包覆。 最後一部分則是將磁性乳膠顆粒進行加熱效果及藥物釋放的測試。透過外加磁場，Fe3O4會因磁滯損耗而產生熱能，若能達到42~43 ℃時，則可具備有過高熱治療的功效。同時，具備有溫度感應性的膠體也會因為磁滯損耗所造成的溫度變化而形成相變化，進而釋放藥物。在功率電流150A，頻率80.53kHz，濃度50 mg/mL的條件下進行加熱效果測試，結果發現磁性乳膠顆粒的加熱效果恰巧介於單純的磁性粒子與乳膠顆粒之間且溫度上升達5~6℃，已大略達到熱治療的需求溫度。而藥物釋放方面則選用靛花青 (Indocyanine Green, ICG) 與亞甲藍(Methylene Blue, MB) 做為藥物來進行釋放模擬。結果發現，利用磁滯損耗的熱能的確可使得膠體產生相變化而有效的釋放藥物，並達到80%~90%的高釋放率。本研究結合磁性奈米粒子的熱損耗以及溫感性微乳膠的溫感性質等兩種材料的特性，以開發新一代藥物治療之載體技術，期待能改善現有藥物載體的負作用並提升藥物釋放的效率。 | zh_TW |
| dc.description.abstract | This study is divided into four parts. In the first part, the precursors FeCl3．6H2O and FeCl2．4H2O was dissolved in water and then alkali was added to synthesis magnetite nanoparticles by co-precipitation method. The distribution of particle size, surface potential, morphology, lattice structure and magnetic properties of these particles were compared with commercial magnetite. From the results, the size of magnetite were all about 20nm by using different kind’s of alkali. Due to the electric and steric repulsion effect, the size distribution was varied so much, especially the magnetite which used N(CH3)4OH as the alkali. And from the SQUID analysis, the one which use N(CH3)4OH as the alkali could be obtained 60 emu/g magnetization and as higher as the commercial one. According to previous research, the higher the magnetization, the higher the heat efficiency.
At the second part, we used N-isopropylacrylamide (NIPAAM), acrylic acid (AAc) and 2-hydroxyethyl methacrylate (HEMA) as the monomer, N,N’-methylenebis acrylamide (MBA) as the cross-linking agent and Potassium persulfate (KPS) as the initiator to prepare thermoresponsive copolymer microgels by using surfactant-free emulsion polymerization. To reach the goal of the drug delivery temperature, we changed the copolymer molar ratio and further discussed their size distribution, morphology, thermal properties, thermal and pH responsibility. From the the TEM, the size was measured about 500~600 nm；the glass transition temperature changed with different copolymer ratio；low critical solution temperature (LCST) was increasing obviously with increasing HEMA and AAc monomer ratio and then reach the goal of drug releasing temperature-40℃. For pH effect, pH = 7 for HEMA system and pH = 9 for AAc system could get good swelling ratio. NMR spectrum couldn’t be used to calculate the copolymer ratio because some of the characteristic peaks were not find, that may due to the concentration of cross-linking agent was too high. By combining the above two parts , we prepared the magnetic microgels by using some chemical bonding of magnetite and thermoresponsive copolymer microgels. The hysteresis loss effect resulted from applying a magnetic field to the magnetite can be used as the thermoresponsive switch, and thus the drug delivery by microgels can be achieved by the change of its morphology. From TEM and TGA results, we can find that only AAc system could encapsulate the magnetite well by in in–situ because the chemical bonding between carboxylate group and Fe2+ and Fe3+ . Finally, the magnetic microgels was tested on heating and drug delivery. By applying the magnetic field, the magnetite produced heat by hysteresis loss, if the temperature can reach 42~43℃, the magnetic microgels may be used as hyperthermia. At the same time, the thermoreponsive copolymer microgels would change its morphology and release drug by increasing the temperature. Under 150A, 80.53kHz, 50mg/Ml, the temperature increased about 5~6℃ and reach to the goal temperature of hyperthermia for magnetic microgels but not for only thermoresponsive copolymer microgels. Indocyanine Green (ICG) and Methylene Blue (MB) were be choosing as the drug to do the release test. From the results, the heat produced by hysteresis loss could be used as the temperature switch and release drug about 80~90% of total quality of drug. .We hope this study can combine the properties of two materials to develop the new therapy technology and improve the side effect of drug loader and increase the drug releasing efficiency. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T00:11:45Z (GMT). No. of bitstreams: 1 ntu-96-R94549006-1.pdf: 5794505 bytes, checksum: 31b78d2a637de37dc12630e21a4fa6f1 (MD5) Previous issue date: 2007 | en |
| dc.description.tableofcontents | 中文摘要………………………………………………………………I
英文摘要……………………………………………………………….III 目錄…………………………………………………………………VII 表目錄………………………………………………………………….XII 圖目錄………………………………………………………………...XIV 第一章 緒論…………………………………………………………….1 1-1前言...……………………………………………………...1 1-2磁性理論...………………………………………………...2 1-2-1磁性單位..…………………………………………...2 1-2-2磁滯曲線..…………………………………………...3 1-2-3磁性物質種類………………………….....................5 1-3磁性材料…………………………………………………..8 1-3-1鐵氧化物……...…………………………………...8 1-3-2磁性奈米材料之應用………………………………9 1-4環境敏感性高分子...……………………….................12 1-5乳化聚合...…………………………………..................15 第二章 文獻回顧與研究目的……………………………….......17 2-1磁性流體與鐵氧化物之製備與性質......................17 2-1-1磁性流體的製備……………………………………17 2-1-2鐵氧化物的製備與性質…………………………...20 2-2溫感性乳膠顆粒之製備與其性質及工作原理…………24 2-2-1微乳膠簡介…………………………………………24 2-2-2乳化聚合之原理與反應機構……………………….27 2-3過高熱治療技術…………………………………………32 2-3-1 熱治療技術之機制…………………………………33 2-3-2 熱治療技術之方法與媒介…………………………37 2-3-3 熱治療技術之熱損效率及原理……………………41 2-4 藥物控制釋放技術………………………………………45 2-5研究動機與目的…………………………………………48 2-6研究架構…………………………………………………50 第三章 實驗……………………………………………………………51 3-1實驗藥品…………………………………………………51 3-2實驗儀器…………………………………………………53 3-3實驗流程…………………………………………………55 3-3-1鐵氧化物奈米顆粒之製備流程……………………55 3-3-2溫感性乳膠顆粒之製備流程………………………55 3-3-3磁性溫感性乳膠顆粒之製備流程…………………56 3-3-4 (磁性)溫感性乳膠包覆藥物之製備流程…………56 3-4製備方法…………………………………………………57 3-4-1鐵氧化物奈米顆粒之製備…………………………57 3-4-2溫感性乳膠顆粒之製備……………………………58 3-4-3磁性溫感性乳膠顆粒之製備………………………59 3-4-4 (磁性)溫感性乳膠包覆藥物之製備…………….…60 3-5性質測定與分析…………………………………………61 3-5-1粒徑與Zeta potential表面電荷分析………………61 3-5-2晶格繞射分析(XRD)………………………………61 3-5-3超導量子干涉儀分析(SQUID)……………………61 3-5-4穿隧式電子顯微鏡(TEM)…………………………62 3-5-5熱裂解溫度-熱重損失分析儀分析(TGA)…………62 3-5-6玻璃轉移溫度-熱微差分析儀分析(DSC)…………62 3-5-7 LCST(UV and DLS)分析………………………….62 3-5-8乳膠顆粒之pH值感應性分析……………………63 3-5-9超導核磁共振儀(NMR)……………………………63 3-5-10熱治療效果測試………………………………….63 3-5-11藥物釋放模擬……………………………...............63 第四章 結果與討論……………………………………………………67 4-1鐵氧化物奈米顆粒的合成………………………………67 4-2溫感性乳膠顆粒的合成…………………………………69 4-3磁性溫感性乳膠顆粒的合成……………………………70 4-4 (磁性)溫感性乳膠顆粒包覆藥物之製備………………...71 4-5粒徑與Zeta potential表面電荷分析結果………………72 4-6晶格繞射分析結果………………………………………75 4-7超導量子干涉儀分析結果………………………………76 4-8穿隧式電子顯微鏡照片…………………………………78 4-9熱裂解溫度-熱重損失分析儀分析結果…………………84 4-10玻璃轉移溫度-熱微差分析儀分析結果………………...87 4-11 LCST(UV and DLS)分析結果………………………….91 4-12酸鹼感應性分析結果……………………………………99 4-13超導核磁共振儀分析結果……………………………102 4-14熱治療效果測試結果…………………………………112 4-15藥物釋放模擬結果……………………………………119 4-15-1 ICG檢量線之建立……………………………..119 4-15-2 MB檢量線之建立………………………………120 4-15-3 藥物包覆釋放測試及膨潤性測試…………..…123 第五章 綜合討論……………………………………………..………135 第六章 結論與建議…………………………………………………139 6-1結論………………………………………………………139 6-2建議……………………………………………………..142 第七章 參考文獻……………………………………………………143 附錄A …………………………………………………………………159 | |
| dc.language.iso | zh-TW | |
| dc.title | 溫度感應性共聚微乳膠與磁性材料結合應用於熱治療與藥物釋放系統之研究 | zh_TW |
| dc.title | Combining of Thermoresponsive Copolymer Microgels and Magnetic Materials for Used in Hyperthermia and Drug Delivery systems | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 95-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 周澤川(Tse-Chuan Chou),楊明長(Ming-Chang Yang),邱文英(Wen-Yen Chiu) | |
| dc.subject.keyword | 丙烯酸,共聚溫感性微乳膠,共沉澱法,藥物釋放,甲基丙烯酸二羥基乙酯,過高熱治療,氮-異丙基丙烯醯胺, | zh_TW |
| dc.subject.keyword | acrylic acid,copolymer microgels,co-precipitation method,2-hydroxyethyl methacrylate,hyperthermia,N-isopropylacrylamide,thermoresponsive drug delivery, | en |
| dc.relation.page | 162 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2007-07-29 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 高分子科學與工程學研究所 | zh_TW |
| 顯示於系所單位： | 高分子科學與工程學研究所 | |
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