本研究以氣相電泳法 (the gas-phase electrophoretic approach) 為基礎，開發生醫奈米材料分析鑑定之儀器技術與方法，藉由電噴灑式電移動度粒徑分析儀 (electrospray-differential mobility analyzer, ES-DMA) 和氣溶膠粒子重量分析儀 (aerosol particle mass analyzer, APM) 來量測生醫奈米材料分散於溶液相的電移動度粒徑分佈、重量分佈、濃度、膠體穩定性等性質，並藉由這些資訊可進一步探討其在水溶液環境中發生的反應與其動力學。
首先在研究的第一部分，我們利用 ES-DMA 開發一套快速且具高解析度的分析方法來定量的鑑定玻尿酸 (hyaluronic acid, HA) 和研究其交聯反應。利用 ES-DMA 之分析技術我們可以成功得到 HA 的電移動度粒徑分佈、數量濃度、分子量分佈、多分散性指數 (polydispersity index, PDI) 等參數。同時，粒徑篩析層析法 (Size exclusion chromatography, SEC) 則被用來當作一個與 ES-DMA 相互比較的分析方法，實驗結果指出在半定量的基礎上，以ES-DMA 量測出 HA 的平均分子量和 PDI 值與 SEC 分析的實驗結果是接近的。除上述 HA 基本性質之外，經由隨時間的量測並追蹤 HA 與 1,4-butanediol diglycidyl ether (BDDE) 的交聯反應也能夠被成功地鑑定，根據實驗結果 HA 和 BDDE 交聯的反應程度與反應速率和反應溫度與 BDDE/HA 濃度比值呈現正相關性。根據實驗結果並在 Smoluchowski 聚集模型下，BDDE 與 HA 交聯反應的活化能為 ≈21 kJ/mol。此研究顯示，我們成功開發以 ES-DMA 為基礎之新的量測方法來快速且定量的鑑定 HA 與其衍生的產品，並能提供即時量測監控的能力來應用在 HA 交聯反應的配方製程上。
在研究的第二部分，利用氣相電泳法以 ES-DMA 和 APM 的分析技術，我們可以量測金屬－有機框架 (Metal-organic framework, MOF) 應用在藥物載體系統之載藥前後電移動度粒徑分佈與粒子重量分佈的變化，並探討其膠體結構穩定性、藥物擔載量、及藥物釋放狀況等等。在此我們選用 UiO-66-NH2¬ 和布洛芬 (Ibuprofen, Ibu) 分別當作代表性的 MOF 藥物載體及代表性的藥物分子，並利用 ES-DMA/APM 來分析此藥物載體系統。以此方法我們成功量測到 UiO-66-NH2 的載藥量(≈55 mg的布洛芬/g 的 UiO-66-NH2)，且在酸性磷酸鹽緩衝液的環境下，UiO-66-NH2 的結構穩定性和布洛芬的釋放也可以被量測出來。此開發量測方法提供一個概念的證明：對於以 MOF 為基礎的原料藥物載體系統，可以利用此方法直接量測分析 MOF 藥物載體系統之性質與狀態，對其相關研究有所幫助。
本研究開發氣相電泳式分析方法來量測應用於生醫領域之奈米材料，藉由此分析方法即時得到與材料相關之資訊，對於其不管在實際應用或是研究上的配方化學是有用的。

In this study, we develop the characterization method and technique to analyze the biomedical nanomaterials using the gas-phase electrophoretic approach. The mobility size distributions, particle mass distributions, number concentrations and colloid stability of biomedical nanomaterials dispersed in colloid can be successfully characterized by electrospray-differential mobility analyzer (ES-DMA) and aerosol particle mass analyzer (APM). Based on the change of the materials properties shown above, we can investigate the reactions and its kinetics occurring in solution.
In the first part of this work, we report a facile, high-resolution approach to quantitatively characterize hyaluronic acid (HA) and study its crosslinking reaction using electrospray-differential mobility analysis (ES-DMA). Mobility size distributions, number concentrations, molecular mass distributions and polydispersity index of HAs were able to be successfully characterized by ES-DMA. Size exclusion chromatography (SEC) was employed as an orthogonal approach, showing that averaged molecular mass and polydispersity index of HA measured by ES-DMA were close to the results of SEC on a semi-quantitative basis. The 1,4-butanediol diglycidyl ether (BDDE)-induced crosslinking of HA was also able to be successfully characterized through a time-dependent study. Both the extent and the rate of HA-crosslinking (induced by BDDE) were proportional to reaction temperature and concentration ratio of HA to BDDE. The activation energy of the BDDE-induced crosslinking of HA was found to be ≈21 kJ/mol. The prototype study demonstrates ES-DMA as a new method for a rapid quantitative characterization of HA and its derivative product and providing a capability of real-time monitoring of the HA-crosslinking during formulation process.
In the second part of this work, we characterize the mobility size distributions and particle mass distributions of metal-organic framework (MOF) before and after the drug loading using ES-DMA and APM. The loading capacity, structural stability, and ibuprofen release can be obtained through this methodology. A successful quantification of ibuprofen loading in UiO-66-NH2 (i.e., the representative drug molecule and MOF, respectively) achieved based on the aerosol particle mass of MOF measured by ES-DMA/APM (≈55 mg of ibuprofen/g of UiO-66-NH2). Structural stability of UiO-66-NH2 versus ibuprofen release was successfully quantified over a 7-day period in an acidic phosphate buffer solution. The methodology provides a proof-of-concept scheme for controlled release studies of different types of active pharmaceutical ingredient from a variety of MOF-based nanocarrier systems.
This study demonstrates a facile methodology to determine some important factors of biomedical nanomaterials, which can be useful for formulation process in practical and research applications.

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