磁性奈米脂粒之製作與其溫控藥物制放特性之研究

Iron-Oxide Embedded Solid Lipid Nanovesicles for Magnetically Controlled Hyperthermia and Drug Delivery

許銘晃(Ming-huang Hsu)

指導教授 ： 蘇育全

國立清華大學/原子科學院/工程與系統科學系/碩士(2007年)

摘要

藥物在輸送過程中會無法輸送病變部位或是還未到病變部位就已被代謝或釋放的顧慮，如此會對病變部位以外的正常細胞造成不必要的傷害，導致產生掉髮、頭暈及嘔吐等現象；以藥物載體承載藥物可降低傷害並且增加藥物療效及減少用藥劑量。本論文主要目標是開發可控制藥物釋放的磁性奈米藥物載體。並且探討利用交變磁場加熱載體的可行性與加熱對載體內部藥物的釋放速度之影響。本研究利用高壓均質機製備粒徑為奈米等級的藥物載體，載體由固態脂質Trilaurin與界面活性劑Poloxamer 188所組成，載體內部承載親油性藥物Tetracaine與表面接上親油性官能基(Fe-O)3-Si-C18的超順磁性奈米氧化鐵粒子。利用超順磁性奈米氧化鐵粒子在交變磁場內產熱之特性，將含有超順磁性奈米氧化鐵粒子的載體放入高強度與高頻率的交變磁場中升溫，當載體溫度達到45℃以上載體由固態轉為液態時，載體內部藥物會加速擴散速度。本實驗已製作出粒徑為150nm的藥物載體，並且在25KHz頻率與700G強度的磁場可將承載21mg/ml超順磁奈米氧化鐵的載體由37℃加熱到50℃。我們在20分鐘後觀察到約有30％藥物釋放到外界水相當中。未來目標則是建構出更快速的藥物釋放系統，且可適用於不同極性藥物的整合性藥物載體，更大大的提升藥物的療效與減少藥物的劑量。

關鍵字

固態脂質 ； 超順磁性 ； 藥物傳輸

並列摘要

This thesis presents the development of magnetic lipid nanoparticles can serve as controlled delivery vehicles and release encapsulated drugs in a desired manner. The nanovesicles are composed of multiple drugs and lipids, which are solid at body temperature while melted around 45 to 55 °C. In addition, super-paramagnetic g-Fe2O3 particles with diameters ranging from 5 to 25 nm are surface modified and dispersed uniformly in the lipid nanovesicles. In the prototype demonstration, lipid nanovesicles with average diameters between 100 and 150 nm were fabricated by high-pressure emulsification processes at raised temperatures. When exposed to an alternating magnetic field of 60 kA/m at 25 kHz, a solution with 2 g/L g-Fe2O3 showed a temperature rise from 37 to 50℃in 20 minutes. Meanwhile, the dissipated heat melted the lipids and resulted in an accelerated release of encapsulated drugs. It was verified that roughly 35% of the encapsulated drug (Tetracaine) was released from the nanovesicles. As such, the presented lipid nanovesicles pioneer a new scheme for magnetically control of heating and drug delivery, which could greatly enhance the performance of associated drugs.

並列關鍵字

solid lipid nanoparticles ； superparamagnetic ； drug delivery

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