本論文主要可分為三個部分，第一部分為引進微流道反應器製備微球體。利用微流道反應器內油相切割水相，使水相被切割成微球體形狀，同時間水相中的海藻酸鈉與油相中的鈣離子交聯，在油水交界面形成海藻酸鈣，以保持微球體形狀，並探討利用不同油/水相流率，控制微球體的直徑。第二部分為探討海藻酸鈣微球體的包覆能力。將四氧化三鐵 (Fe3O4) 磁性金屬粒子、綠色螢光牛血清蛋白 (green fluorescent bovine serum albumin, GFP)、L-929老鼠纖維母細胞、磺胺嘧啶銀 (AgSD)、以及薑黃素等與水相混合後，以此水相製備海藻酸鈣微球體，並根據包覆物的性質進行相關測定。第三部分為探討海藻酸鈣微球體的釋放性質。以薑黃素作為釋放對象，先以帶有不同電荷的界面活性劑增加薑黃素水溶解度，再將薑黃素包覆於微球體，並探討改變在不同釋放環境下、不同包覆量及不同微球體數目對薑黃素釋放之影響。
於論文第一部分中，為最適化微流道系統製備海藻酸鈣微球體，利用傅立葉轉換紅外光譜儀 (Fourier Transform Infrared Spectrometer, FTIR) 分析加入氯化鈣的油酸溶液，發現羧基與鈣離子鍵結所產生 (COO-Ca) 鍵結，證明油酸成功與氯化鈣鍵結。由光學顯微鏡觀測當固定水相中海藻酸鈉濃度2 w/v%，而油相中氯化鈣濃度從0.1增至1 w/v%，可發現碎片量下降且微球體直徑變小及均一性提高。當改變油水相流率於0.02至0.5 ml/min之間，利用光學顯微鏡觀測可發現微球體直徑介於63至2314 µm。結果指出此系統可以成功製備海藻酸鈣微球體並調整其直徑。
於論文第二部分中，為探討海藻酸鈣微球體的包覆能力。利用海藻酸鈣微球體包覆 (i) Fe3O4、(ii) GFP、(iii) L-929老鼠纖維母細胞、(iv) AgSD、以及 (v) 將黃素，並探討微球體的性質變化。由光學顯微鏡可觀測到經微球體包覆後直徑增加；由FTIR分析可得包覆後會出現包覆物的特徵峰；由磁鐵的磁性測是可觀測到包覆Fe3O4¬後微球體受到磁鐵吸引；由螢光顯微鏡可觀測到包覆GFP後微球體能具有綠色螢光；由乳酸脫氫酶呈色分析法 (LDH assay) 可觀測到經一天細胞培養，微球體的細胞數目從5000增至25000 cell。結果指出海藻酸鈣微球體可以包覆不同類型的材料並保有材料的原性質。
於論文第三部分中，為探討微球體包覆薑黃素對薑黃素釋放之影響，為了解決薑黃素底水溶解度的問題，本研究選擇四種帶有不同電荷的界面活性劑: Triton X-100、Tween 20、cetyltrimethylammonium chloride (CTAC)、sodium dodecyl sulfate (SDS)，其電荷依序為: 中性、中性、正電、負電，探討不同界面活性劑及電荷對微球體包覆薑黃素的影響。由光學顯微鏡可觀測到Tween 20以及CTAC可成功製備出微球體形狀，而Triton X-100以及SDS分別為拖尾球體及柱狀。從FTIR可觀測到油酸以及與海藻酸鈣重疊而不明顯的薑黃素特徵峰。從XRD可觀測到薑黃素因為被界面活性劑形成的微胞包覆，因此從具有晶型變成無非晶型複合物。從TGA可觀測到Tween 20與CTAC在500℃殘餘重量與海藻酸鈣依序有1.52、1.08 %差異，此為薑黃素含量。綜合以上結果選擇Tween 20作為薑黃素釋放探討組別。薑黃素釋放結果顯示Tween 20為可調整釋放速度的載體，且從Korsmeyer-Peppas與Kopcha可得知釋放機制為同時存在擴散與侵蝕相，並以擴散相為主要機制。

The versatility of a microfluidic reactor was demonstrated in this thesis by applying this technique to synthesize microspheres. In the first part, microfluidic reactor was used to prepare microspheres (MS). The formation of MS were initiated when the oil phase met an aqueous phase in a cross region of the microfluidic reactor. Afterward, MS would become a hydrogel because of the crosslink reaction between sodium alginate and calcium chloride at the interface between oil and aqueous phases, which kept the round shape of microsphere. In the second part, the encapsulation of different types of materials into MS were investigated and the resulting materials were characterized. Finally, in the third part, the encapsulation of four different charges of surfactants to improve the solubility and loading amount of curcumin in the MS were studied for drug release application.
In the first part, MS were prepared by a microfluidic reactor with optimized parameters. The chemical functional group of MS was characterized by Fourier Transform Infrared spectroscopy (FTIR). The results showed that the characteristic peaks of carboxyl and calcium ions existed which indicates that oleic acid was successfully conjugated with calcium chloride. From optical microscopy (OM) image, the amount of fragment decreased and the diameters of MS became smaller and more uniform with increasing the concentration of CaCl2 from 0.1 to 1 w/v%. The diameters of microspheres could be manipulated from 63 to 2314 m when the flow rates of oil and aqueous phase were varied between 0.02 and 0.5 ml/min. Therefore, microfluidic reactor can prepare calcium alginate microspheres with different diameter sizes.
The second part of this thesis is to investigate the encapsulation ability of as-prepared MS. The characteristics of the encapsulation of several materials: (i) Fe3O4, (ii) GFP, (iii) L-929 mouse fibroblast cell, (iv) silver sulfadiazine (AgSD), and (v) curcumin into MS were studied. From the OM image and FTIR spectra analyses, the diameters of MS increased after the encapsulation of as-studied materials and characteristic peaks which belong to the encapsulation are present. From the magnetic tests, the MS loaded with Fe3O4 can be attracted by a magnet. From fluorescent images, the MS loaded with GFP exhibited a green color. The result of the lactate dehydrogenase (LDH) assay showed that the cell number of MS increased from 5000 to 25000 after one day of culture inside the MS. Therefore, the as-prepared MS were able to encapsulate different types of materials.
In the third part of this work, the release properties of curcumin loaded into MS were examined. In order to solve the limitation of curcumin poor solubility in water, four types of surfactants were investigated: Triton X-100、Tween 20、cetyltrimethylammonium chloride (CTAC)、and sodium dodecyl sulfate (SDS). From the morphology analysis by OM, the morphology of MS with Triton x-100, Tween 20, CTAC and SDS varied from microspheres to microspheres, microspheres with tails, and cylinder, respectively. From the FTIR spectra, the characteristic peaks belonging to oleic acid and curcumin existed, showing the successful incorporation of curcumin into the MS. From the X-ray diffraction (XRD) spectra, the crystallinity of curcumin showed an amorphous structure after mixed with surfactants and encapsulated inside the MS. From thermogravimetric analysis (TGA) curves, the difference of residue weight compared MS with MS contain Tween 20 or Triton and curcumin at 500℃ which represented to the loading amounts of curcumin were 1.52 % and 1.08 %, respectively. According to the result, Tween 20 was chosen to study the release profiles of curcumin in PBS buffer. The results of curcumin release showed that MS with Tween 20 were the carriers with adjustable release rate. The drug release mechanism was found to be the simultaneous diffusion and erosion where diffusion was the main mechanism from the mathematical simulation of the Korsmeyer-Peppas and Kopcha models.

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