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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 何佳安(Ja-an Annie Ho) | |
dc.contributor.author | Chun-Ying Wei | en |
dc.contributor.author | 魏君穎 | zh_TW |
dc.date.accessioned | 2021-05-16T16:28:39Z | - |
dc.date.available | 2018-09-06 | |
dc.date.available | 2021-05-16T16:28:39Z | - |
dc.date.copyright | 2013-09-06 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-19 | |
dc.identifier.citation | (1) http://www.doh.gov.tw/CHT2006/DM/DM2_p01.aspx?class_no=25&level_no=1&doc_no=84788 (Accessed July, 2003)
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/6412 | - |
dc.description.abstract | 多數的抗癌藥物,由於其化學結構之疏水性導致生物體的吸收不佳,造成患者在接受癌症化學治療時,藥物達到病灶的有效劑量偏低。為了使累積在病灶處的藥物劑量具實際療效,目前臨床醫師的做法是讓病患提高服用藥物的濃度,但此舉卻造成不可避免的化療副作用。近年來,眾多研究都希望能夠利用藥物傳遞系統的設計,發展出多功能、智慧型的奈米藥物載體,其目的即在解決現今臨床醫學所遇到的上述難題。
有鑑於此,本研究的動機與目的即在設計出以蓖麻油及12-羥基硬脂酸為主成份,利用自組裝方式,形成具生物相容性的膠態三維纖維結構,並以磷脂質修飾構成穩定的膠體溶液系統。該奈米三維纖維結構可同時包覆抗癌藥物(喜樹鹼)及磁性氧化鐵奈米粒子於其中,形成熱敏感性的藥物載體;若對其施以高頻變化的磁場,可使磁性氧化鐵奈米粒子產生磁熱效應釋放出熱能使侷域溫度上升,當溫度達到44 oC時,此熱敏感載體會產生相轉變成溶膠態,即可快速並有效地釋放出藥物。此外,由於溫熱療法對癌細胞的殺傷力較正常細胞大,故此熱敏感載體亦可同時抑制癌細胞生長的效率。 本研究亦對該熱敏感載體進行相關定性分析;以動態光散射儀測得其粒徑大小約260 nm,界面電位為-55 mV,相變溫度為44oC,輔助磁場33.9 kA/m及頻率33.9 kHz條件下其損耗功率值為 369 W/g Fe;此外,該載體亦具磁振造影T2顯影劑之功能。初步in vitro實驗證實,此熱敏感載體不具生物毒性,且表面修飾具有標靶特性的分子(如葉酸)能成功的對葉酸過量表現的癌細胞(HeLa)進行選擇性的靶向傳遞。此熱敏感載體應可在in vivo模式中被再次證實其化療及溫熱治療之協同效應。 | zh_TW |
dc.description.abstract | More than 50% of anti-cancer drugs obtained directly from synthesis have poor water solubility. Loading of the hydrophobic drug into nanocarriers, followed by delivery of the carriers to the site of desired action and subsequent release of the encapsulated drugs in situ is one common approach to circumvent the aforementioned problem. Passive targeted delivery system keeps circulating in the blood stream and allows itself to be taken to the target receptor; passive release of drug payload, however, is commonly observed with conventional drug delivery nanosystems, restraining their capability of discharging drugs on an effective concentration at a desired time window. Compared to passive targeting/passive releasing strategy, active targeting (such as receptor-mediated approach)/controllable release mechanism may further enhance the efficacy of drug delivered by nanovehicles.
Hyperthermia is one clinical protocol used as co-adjuvant therapy for cancer treatment. A clear synergistic effect was described previously when combined with radiotherapy, as well as increase efficacy of chemotherapy. Magnetic hyperthermia using ferrite nanoparticles has recently emerged as a promising approach for cancer therapy. Magnetic nanoparticles, serving as a therapeutic agent, a heat nanomediator or a MRI contrast agent, gained significant popularity in recent years due to their superparamagnetic properties. Taking advantage of the potential benefits of nanotechnology, a biocompatible nanocarrier for controlled releasing entrapped hydrophobic drugs was designed and developed herein. The novel nanocarrier was prepared via nanoemulsion method by sonicating 12-hydroxystearic acid (12-HSA)/castor oil/phospholipid (DPPC, DPPG, DSPE-PEG2000-folic acid) mixture in a phosphate buffered saline solution (PBS), followed by the formation of a nanoshuttle composed of an inner gel core and an outer phospholipid shell. Camptothecin (CPT, selected herein as a model drug) or superparamagnetic iron oxide nanoparticles (SPIONs, a heat generator), could be loaded either individually or concurrently into the core of the nanoshuttle by dissolving either/both hydrophobic CPT or/and oleic acid-coated SPIONs in the oil phase before nanoemulsion. Results showed that the as-prepared nanoshuttles were stable up to 7 days with an average hydrodynamic of 260 nm, surface charge of -55 mV and a phase transition temperature of 44oC. Transmission electron microscopic analyses revealed that our (phospholipid-gel-SPIONs)PLG-SPION nanoshuttles contained multiple 10-nm-sized SPIONs encapsulated in gel network, surrounded by phospholipid layer. It was also confirmed that the PLG-SPIONs nanoshuttles exhibited superior magnetic heating ability with specific loss power (SLP) value 369 W/gFe. Cytotoxicity study was also carried out to verify the biocompatibility of the PLG-SPIONs nanoshuttles. In addition, our PLG-CPT/SPIONs nanoshuttles (both CPT and SPIONs were loaded into PLG particles) demonstrated excellent efficacy in inhibiting the proliferation of HeLa cells. Taken all together, our PLG-CPT/SPIONs nanoshuttles hold the great potential for the development of innovative biomedical applications such as targeted drug delivery, tumor heating and in vivo contrast agents, and eventual expansion into possible alternative approach for cancer treatment. | en |
dc.description.provenance | Made available in DSpace on 2021-05-16T16:28:39Z (GMT). No. of bitstreams: 1 ntu-102-R00b22025-1.pdf: 2963158 bytes, checksum: 65b973549d624416e8bfe54602127d21 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 謝誌 i
中文摘要 ii Abstract iv 圖目錄 ix 表目錄 xiii 第一章 緒論 1 第二章 文獻回顧 6 2.1 藥物傳遞系統 (Drug delivery system, DDS) 6 2.2.1 奈米藥物 (Nano-drug, DoxilR) 8 2.2.2 抗癌藥物-喜樹鹼 (Anticancer drug - camptothecin, CPT) 9 2.2 靶向藥物傳遞系統 (Target drug delivery system) 10 2.2.1 葉酸與葉酸受體 (Folate and folate receptor) 11 2.2.2 控制釋放 (Controlled release) 15 2.3 藥物載體使用之材料 (Materials) 16 2.3.1 磷脂質修飾奈米藥物載體 (Phospholipid-capped nano drug carrier) 16 2.3.2 熱敏感膠體奈米粒子 (Thermo-sensitive nanoparticle) 19 2.3.3 磁性奈米粒子 (Magnetic nanoparticle) 21 2.4 電磁感應溫熱療法 (AC magnetic hyperthermia) 24 2.4.1 磁流體熱療 (Magnetic fluid hyperthermia) 25 2.5 結語 27 第三章 實驗藥品與儀器 28 3.1 實驗藥品 (Chemicals and reagents) 28 3.2 實驗儀器 (Apparatus) 30 3.3 癌細胞株 (Cancer cell lines) 31 第四章 製備方法與鑑定 32 4.1 數學計算蓖麻油與磷脂質之重量比值 (Mathematical calculation the mass ratio of castor oil and phospholipid) 32 4.2 熱敏感藥物載體之製備 (Preparation of phospholipid-gel-superparamagnetic iron oxide nanoparticles, PLG-SPIONs nanoshuttle) 33 4.2.1 實驗材料 33 4.2.2 使用儀器 33 4.3 合成控制變因及應變變因 (Variable factors of synthetic process) 34 4.3.1 調整親脂性溶劑:水相溶液體積比 34 4.3.2 超音波震盪時間 35 4.3.3 改變針筒注射泵之流速 36 4.3.4 最佳化合成方法與條件 36 4.4 純化分離 (Purification and separation) 37 4.4.1 離心方法一 37 4.4.2 離心方法二 37 4.4.3 離心方法三 37 4.5 界面電位值 (Zeta-potential) 39 4.6 穿透式電子顯微鏡圖 (TEM image) 40 4.7 塊材相變溫度圖 (Phase transition of bulk material) 43 4.8 示差掃描熱卡計圖 (Differential scanning calorimetry, DSC profiles) 44 4.9 加熱曲線圖 (Heating profile) 46 4.10 損耗功率值 (Specific loss power, SLP value) 47 4.11 T2 顯影圖 (In tube T2-weighted imaging) 48 4.12 藥物釋放曲線圖 (In tube drug release profile via direct heating) 49 4.13 藥物包覆率之計算 (Encapsulation efficiency percentage of CPT) 50 4.14 免疫試片呈色反應 (Membrane strip immunoassay of anti-folate v.s. anti-biotin) 51 4.15 In vitro 實驗 (In vitro experiments) 52 4.15.1 實驗材料 52 4.15.2 實驗組別 52 4.15.3 熱敏感載體對細胞之毒性 53 4.15.4 包覆喜樹鹼之熱敏感載體其細胞存活率 54 第五章 結果與討論 55 參考文獻 56 | |
dc.language.iso | zh-TW | |
dc.title | 兼具熱敏感性及標靶功能之藥物載體在癌症治療及生醫影像之應用 | zh_TW |
dc.title | Thermo-sensitive, targeted delivery nanoshuttle with dual-function in improved chemotherapy and MRI imaging | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 廖明淵(Ming-Yuan Liao),吳立真(Li-Chen Wu) | |
dc.subject.keyword | 藥物傳遞系統,靶向傳遞系統,熱敏感性藥物載體,膠態三維纖維結構,磁場誘導磁熱效應,溫熱療法,磷脂質, | zh_TW |
dc.subject.keyword | thermo-sensitive nanocarrier,targeted drug delivery,phospholipid-capped nanosystem,AC magnetic hyperthermia, | en |
dc.relation.page | 68 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2013-08-19 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
顯示於系所單位: | 生化科技學系 |
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