聚縮酮（Polyketal, PK）常用乳化溶劑蒸發技術(Emulsion-solvent evaporation, ESE)製備顆粒，因具有酸敏感性且產生中性的降解產物，不會引起免疫反應，在藥物釋放被廣泛的應用。在本研究中，我們利用靜電紡絲（electrospinning）製備聚縮酮/聚乳酸（poly lactic acid, PLA）微米串珠(bead-on-string)纖維，並分析微米串珠纖維的物理性質、釋放行為和生物相容性(biocompatibility)。
我們使用逐步聚合法(step-growth polymerization)進行縮酮反應，合成PK共聚物，再將PK/PDLLA（Poly(D,L-lactic acid),PDLLA）和PK/PLLA（Poly(L-lactic acid),PLLA）的共混物，通過靜電紡絲製備出PK/PDLLA和PK/PLLA 微米串珠纖維。透過掃描式電子顯微鏡照片，我們得知串珠的比例會隨著電壓的提高、工作距離的減少與PK含量的提高而增加，由於串珠納米纖維中的串珠是裝載藥物的主要位置，因此，串珠數量是串珠纖維包封能力的重要因素之一。在所有的參數中，調整PK/PDLLA和PK/PLLA的重量比是調整材料型態最為有效的方法，因此，我們將利用不同PK/PDLLA和PK/PLLA的重量比來進行材料特性測試與細胞實驗，其他參數固定於可以穩定的進行靜電紡絲並得到最高串珠比例的條件(電壓10kV、流速0.2ml/hr、工作距離10cm、PK/PDLLA和PK/PLLA在二氯甲烷(dichloromethane, DCM)中的濃度分別為89mg/ml (8wt%) 和44.5mg/ml (4wt%)。
當PK含量夠高時(PK-PDLLA2:1、PK-PDLLA1:1)，PK/PDLLA微米串珠纖維保留了PK微米顆粒的pH敏感性。相比之下，在PK/PLLA微米串珠纖維實驗中，雖然PK-PLLA2:1時仍保留了PK微米顆粒的pH敏感性，但因為PLLA比PDLLA更為疏水且降解時間更長，所以pH對膨潤及重量損失的影響程度比PK/PDLLA系統低。
我們在PK/PDLLA和PK/PLLA微米串珠纖維中包覆亞甲基藍(methylene blue)以進行控制釋放實驗。釋放曲線表明當PK/PDLLA和PK/PLLA共混物被製備成微米串珠纖維後，當PK在PK/PDLLA系統中的含量足夠時，藥物釋放呈現明顯pH敏感性，此結果與膨潤性的結果相呼應。相對地， PK/PLLA的pH敏感性影響沒有明顯的表現出來，此結果可能是因為PLLA較為疏水，使得PK/PLLA共混物中的PK不易與外界環境中的水接觸而產生反應。過去的文獻中，在pH=4.5的環境下，純PK粒需6小時累積釋放值才能達到總量的50%，與本研究中PK含量高的PK/PDLLA微米串珠纖維(PK-PDLLA2:1)進行藥物釋放結果的比較，在30分鐘時累積釋放值就能達到總量的82%，因此快速釋放時PK-PDLLA2:1微米串珠纖維具有較佳的優勢。
細胞培養的結果證實含PK的微米串珠纖維具有良好的生物相容性，根據以上結果，本研究開發的PK/PDLLA和PK/PLLA 微米串珠纖維具有pH敏感性與良好的生物相容性，有潛力成為治療急性炎症疾病的藥物載體。

PK is often used to prepare particles by emulsion process. Because of its acid-sensitivity and neutral degradation products, PK doesn’t cause any immune response and is thus widely applied in drug delivery. In this study, polyketal/ poly lactic acid bead-on-string microfibers were prepared by electrospinning processes, where the physical properties, release profile and biocompatibility of microfibers were analyzed.
PK was synthesized via the acetal exchange reaction. PDLLA and PLLA were blended with PK to prepare bead-on-string microfibers by electrospinning. According to SEM images, the proportion of beads increased with the increase of voltage, the reduction of working distance and the increase of PK content. As beads in bead-on-string nanofibers were the main reservoirs to load drugs, bead number is one of important factors to indicate the encapsulation capability of the bead-on-string fibers. Among all the parameters, adjusting the weight ratio of PK/PDLLA and PK/PLLA is the most effective way to get different ratio of beads. Therefore, we are going to use different weight ratio of PK/PDLLA and PK/PLLA to test the characteristics of materials and MTT assay. In the experiment, other optimized paramaters are fixed under the conditions that can stably carry out electrospinning and obtain the highest ratio of beads (voltage: 10kV, flow rate: 0.2ml/hr, working distance: 10cm, concentration: 89mg PK/PDLLA /ml dichloromethane (8wt%) and 44.5mg PK/PLLA /ml dichloromethane (4wt%).
The results of swelling and weight loss test showed that PK-PDLLA and PK-PLLA bead-on-string microfibers was pH sensitive as PK particles when the content of PK was sufficient (PK-PDLLA2:1, PK-PDLLA1:1). The pH-dependent swelling and weight loss of PK/PLLA microfibers was lower than PK/PDLLA due to the hydrophobic of PLLA.
The release experiment was carried out by loading methylene blue in PK/PDLLA and PK/PLLA bead-on-string microfibers. The releasing result indicated that when the content of PK was sufficient (PK-PDLLA2:1, PK-PDLLA1:1), the release of encapsulated drugs was dominated by the pH value, which was corresponded to the findings from swelling. However, the pH sensitivity of PK-PLLA microfibers was not obvious for drug release. It is because the interaction between PK and environmental water was limited by the hydrophobicity of PLLA. In previous researches, pure PK particles took 6 hours to release 50% encapsulated drugs after the low-pH stimuli. On the contrary, PK/PDLLA bead-on-string microfibers (PK-PDLLA2:1) took 30 minutes to release 82% encapsulated drugs, revealing the potential of PK/PDLLA microfibers in pH-responsive controlled release.
The results of cell (7F2) culture confirmed that the PK fibers were biocompatible. According to the pH-sensitivity and biocompatibiliuty, the PK/PDLLA and PK/PLLA bead-on-string microfibers developed in this research would be a promising drug carrier for the treatment of acute inflammatory diseases.

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