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  • 學位論文

電場刺激控制藥物釋放元件之研究

Programmable On-Demand Drug Release Device:An Electro-stimulated Approach

指導教授 : 廖英志

摘要


藥物治療的效果,與藥物釋放的位置及藥物在患處所釋放的濃度有關。一個理想的藥物控制釋放元件,須具備以下條件:適用於廣泛的藥物並能儲存大量的藥物、在“off”的狀態下能夠釋放較少甚至零藥物通量、在“on”的狀態下能夠重複性的控制脈衝式藥物釋放,在釋放的過程中不會對藥物釋放元件產生機械性的破壞及在釋放的過程中可有效地藉由刺激的強度改變釋放速率。 在本研究中我們成功地開發出一種利用電場驅動覆膜式藥物控制釋放元件。此控制釋放元件可廣泛地適用於離子型藥物,可使用的藥物分子量範圍為300~40000 道爾吞。利用電場移動帶電藥物分子的釋放機制,其電場刺激的時間對於釋放量的響應迅速,且可成功控制藥物達到脈衝式藥物釋放系統的效果。本系統採用覆膜式儲藥槽,所製造出的控制釋放元件在釋放過程中,不會對元件的結構產生破壞並可重複脈衝式釋放達4次以上。對於不同細胞毒性層級的藥物,控制釋放元件的釋放速率可以由實驗設計的參數改變,即使用不同類型的阻隔膜使控制釋放速率達到一個數量級的差異(10~100 ng / hr),以符合不同藥物對人體的治療效果。除了藉由實驗設計的參數改變,也可藉由施加不同的外加電壓強度,達到一個數量級(100~1000 ng / hr)的差異之控制釋放速率。此外,也可以藉由設計不同電壓波形,依需求控制釋放速率。在此論文所呈現的系統,對於在生物材料、組織工程、移植科技及生物感測器上有極大的應用潛力。

並列摘要


Drug therapy efficacy depends on therapeutic concentrations of drugs at disease sites. An ideal controlled drug delivery device should safely contain a large quantity of drugs, release little or no drug in the “off ” state, be repeatedly switchable to the “on” state without mechanically disrupting the device, and can actively control release rates. In this thesis, an electro-stimulated membrane-based drug delivery device was developed to release drugs on demand. Drugs over a broad range of molecular weights (300-40000 Da) and different charge properties can be delivered by the same drug delivery approach. Ionic drug molecules were electrically ejected from polyelectrolyte hydrogels into bulk solution in vitro, the response time between electric stimulus and release amounts was fast, and without mechanically disrupting the membrane-based drug delivery device .We showed that the dose of drug delivered across drug delivery device could be tuned by different material of membrane, the strength of applied voltage, and the waveform of applied voltage, allowing for pulsatile drug delivery system of model drug, we could control the release rate at 1 order of magnitude (100~1000 ng / hr) during release processes. The system reported here has great potential for use in biomaterials, tissue engineering, implant technology, and biosensors for biomedical applications.

參考文獻


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