Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3936
標題: 以近紅外光螢光物監測微脂體活體中定點釋放模型
Non-Invasive Monitoring in vivo of Liposome Release by NIR Fluorophore
作者: 李季達
Li, Gi-Da
關鍵字: Temperature-sensitive liposome
感溫微脂體
self-quench
near-infrared (NIR)
自滅潛能
近紅外光
出版社: 生醫工程研究所
摘要: 螢光檢測法可應用於建立以非侵入方式偵測活體中微脂體定點釋放的情形。此螢光物必須具有螢光自滅潛能、近紅外光區之最適激發與螢光及相對較佳的親水性。本研究以感溫微脂體(Temperature-sensitive liposome)包覆自滅濃度的近紅外光區螢光物diglucosamid-SIDAG,使其受溫度變化的刺激後促進此螢光物釋放,進而藉由釋放濃度稀釋所造成的螢光強度變化,模擬微脂粒活體中釋放藥物的模型。 本研究分成三個部分,第一部分為合成diglucosamid-SIDAG及其特性分析。合成之SIDAG吸收波峰位於753 nm,而螢光波峰位於783 nm,在HPLC的測試下以面積積分法求得純度為87.5%;第二部分為SIDAG包覆在感溫微脂體(DPPC:MPPC=9:1)中之活體外感溫釋放表現情形,當包覆50 mM SIDAG之微脂體在40℃水浴槽加熱10分鐘後,釋放量大約包覆總量的60%,30分鐘釋放量大於包覆總量的80%;在第三部分裸鼠活體實驗中,觀察包覆自滅濃度之微脂體(DPPC:MPPC:DSPE-PEG2000=86:10:4)於腫瘤植入物組織內感溫釋放內容物的情形。從實驗結果中得知,包覆50 mM SIDAG之感溫微脂體在水浴40℃加熱10分鐘後,螢光物質於腫瘤區域釋放,使其螢光強度上升到原來的約30~60%。綜合實驗結果,証明可以SIDAG建立感溫微脂體於活體內藥物釋放之模型。
Fluorescence measurement can be applied to establish a non-invasive model for monitoring the topic release of liposome in vivo. It requires a fluorescent contrast agent, which has capability of self-quench, optimal absorption and emission in the near-infrared (NIR) region, and decent hydrophilicity. In this study, the NIR fluorophore, diglucosamid-SIDAG, was encapsulated in temperature-sensitive liposome to simulate the drug payload releasing under the stimulation ambient temperature change. In the first phase of the study, the NIR fluorophore, diglucosamid-SIDAG, was synthesized and characterized. Its absorption maximal wavelength was at 753 nm, and fluorescent maximal wavelength was at 783 nm. The purity of the synthetic product was 87.5% analyzed by the integration of peak area in HPLC. In the second phase, 50mM SIDAG was encapsulated in the temperature-sensitive liposome(DPPC: MPPC = 9: 1)to simulate the drug payload releasing under the stimulation ambient temperature change. 60% of the encapsulation released after 10 minutes. The release efficiency was indicated by the fluorescence increase (dilution induced relieving of fluorescence quench), which reached plateau (exceeding 80% of payload) after heated for 30 minutes from in vitro investigation. In the third phase, the diglucosamid-SIDAG encapsulated liposome(DPPC: MPPC: DSPE-PEG2000 = 86: 10: 4) was injected into the MCF-7 xenograft bearing NU/NU nude mice through the tail vein, and elevated its fluorescent intensity by 30-60% after heated in 40°C water bath for 10 minutes. The preliminary result indicates that the NIR fluorophore has the potential to be applied in simulating the in vivo payload release of liposome.
URI: http://hdl.handle.net/11455/3936
Appears in Collections:生醫工程研究所

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