摘要:近年來,標靶治療已成為癌症治療的新方法。其方法是直接準確地提供高濃度的藥物到特定器官,局部性處理病灶,以避免傳統式口服或靜脈注射高劑量化學藥物對人體其他器官產生的干擾或副作用。一般而言,體內植入式的藥物控制設備通常在藥物塗佈一層聚合物以提供持續且固定的藥物釋放量。然而,臨床植入後,我們只能藉由抽取血液或體液來監控藥物的濃度。為了解決這個問題,我們的目標是製造智慧型的藥物釋放設備,其組成包含了檢測,控制釋放,無線電通信等元件。不但可以監視病人的臨床變化,而且可以根據病人情況控制藥物釋放量。
最新的研究顯示,噴墨技術已可製造生物感測器以檢測微量化學物質。同時,噴墨技術也已被用於用於製造藥物釋放裝置及RFID等微型無線電設備。利用前述這些印刷元件,我們可以組裝兼具無線通訊功能的藥物釋放設備。此外,噴墨技術具備低價格的生產要件,以及極大的客製化靈活性,以滿足各個病人的需要。因此,噴墨技術已廣泛被應用在醫療設備生產上,並有著極高的經濟利潤。
為了完美地結合印刷元件,並加速設計過程,我們將利用計算流體力學及分子模擬來設計藥物釋放裝置設備。我們將以分子模擬設計生物感測器,以加強感測器對環境變化的敏感度。我們並將以計算流體力學模擬藥物在血液中之流態,以瞭解藥物的置放地點和聚合物塗層厚度對藥物釋放率之影響。我們並將設計微型藥物貯存槽以延長給藥時限。印刷微型無線電元件屆時將嵌入到聚合物塗層,並連接到生物感測器,以提供信息收集及回饋。
總之,我們將使用噴墨技術生產智慧型的藥物釋放設備,其功能可以監測病人臨床變化並以無線通訊來控制藥物釋放速率。設計過程中,我們將以計算流體力學和分子模擬來最佳化生物感測器的靈敏度、無線通訊的有效性、以及藥物的控制釋放機制。我們並將與其他研究機構進行跨領域合作,以產生一個新的醫療行業。
Abstract: Site specific therapy has emerged as a potential medical cancer treatment in recent years. The idea is to deliver high concentration drug directly and accurately to treat a specific organ locally so that patients can avoid side effects from the dose elevations associated with oral or intravenous administration. A drug carrier device is usually implanted in the patient, and for the prolong usage, polymeric coatings on top of the drug layer are commonly used as a control release agent. Although such mechanism provides a continuous and constant drug flux, clinical effects of the drug after device implantation are only available by external tests to ensure the drug effectiveness. To address these problems, we aim to create smart drug release devices, which compose of detection, control release, and communication parts, so that one can not only monitor clinical changes in patients but also control the drug flux using the same device.
Recent advances in digital inkjet technology, or so-called drop-on-demand method (DOD), have shown its capability of creating bio-sensors to detect trace amount of chemicals. Same technology has also been used to make polymeric coatings for drug release devices, and to print micro-circuitry, such as RFID, to communicate with external electronic devices. With the combination of these printed parts, a drug release device with wireless communication functions can be assembled with merely an inkjet printer. Moreover, DOD method provides micro-patterning in a large scale at low price with great flexibility for customization to meet patients’ needs. Hence, applying DOD technology on medical device production is technically feasible and financially profitable.
In order to flawlessly integrate printed components and to accelerate the design process, computational fluid dynamics (CFD) combining with molecular simulations will be used to optimize device performance. Screening of biosensor designs will be guided by molecular simulations to enhance the sensitivities of biosensors to the environmental changes, such as drug molecules binding to proteins. Computer simulations for convective diffusion and adsorption of drug molecules in blood streams will be conducted to understand the effects of drug location and polymer layer thickness on release rates. With the help of similar simulations, we will also design micro-depots in the device as reservoirs to increase drug storage and to facilitate drug delivery. Printed electronics, which is connected to the bio-sensors, will then embed in the polymer coating to provide information collection and/or communication devices.
In summary, we suggest using drop-on-demand (DOD) technology for the production of smart drug delivery devices, which are accompanied with bio-sensors to detect clinical environmental changes and remote communication circuits to monitor or control drug release rate externally. We will perform state-of-art design process with the help of computational fluid mechanics and molecular simulations to optimize device performance. Academic studies on the sensitivity of bio-sensors, effectiveness of wireless circuitry, and drug release control mechanisms will inspire numerous ideas for publications. Muti-disciplinary collaboration with other departments in NTU and other world-renown institutes is currently undergoing. We believe that this research will generate a new industrial discipline for medical device production.