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應用天然海藻酸鈉包覆多功能材料於創新藥物傳遞系統之研究 = Research on the application of natural sodium alginate encapsulation for multifunctional materials in innovative drug delivery systems / 鄭余宏.

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摘要註

本論文以海藻酸鈉製造微球技術為重點，分別運用靜電噴霧及微流體晶片控制技術，開發微球包覆之創新藥物傳輸機制。本論文將利用天然聚合物海藻酸鈉作為封裝載體，運用其與二價陽離子反應可交聯形成水凝膠結構的特性，期望達到包覆藥物之目的。靜電噴霧通過將液體從噴嘴噴出並施加高壓電場，來生成微小的液滴，經由與氯化鈣交聯後形成穩定的微球。微流體晶片控制透過在微米級的流道內精確操控油水界面的流體，從而生成均勻的液滴，再與氯化鈣交聯，最終形成穩定的微球。上述兩種方法為本論文製造微球外層包覆結構之技術。後續，本論文中亦使用明膠包覆於微球內，透過異硫氰酸螢光素(Fluorescein isothiocyanate, FITC)，由螢光反應觀察兩種不同製程技術的微球包覆型態。兩種微球技術製造後的藥物傳遞性能，則透過將微球浸泡至漢克培養液(Hank’s Balanced Salt Solution)中的生物降解測試及牛血清白蛋白(Bovine Serum Albumin, BSA)的釋放效果來評估。 經由多次試驗及測試後，本論文已成功利用海藻酸鈉製造出兩種不同型態的微球，第一種為靜電噴霧技術製造的實心微球，由螢光反應結果觀察到微球具有無分層的實心結構，直徑範圍從300μm到450μm不等，粒徑大且結構緊密。在降解測試中，微球在72小時重量損失率達79%，對於BSA釋放率在短期達到17.9%，經過三天後，釋放率達到31%。另一種則利用微流體晶片技術製造，螢光顯微鏡下觀察到，微球具有雙層結構，外層為海藻酸鈉，內層為明膠，直徑集中在100μm至150μm之間，尺寸較小且分佈均勻，在降解與釋放測試中，雙層微球的重量損失率達98%，並在短時間內釋放37%的BSA，長期釋放率則達到45%。比較兩種不同製程的微球優勢，靜電噴霧所製造的 This study focuses on the technology of microsphere fabrication using sodium alginate, employing electrostatic spray and microfluidic chip control techniques to develop innovative drug delivery mechanisms. The study utilizes natural polymer sodium alginate as an encapsulation carrier, leveraging its ability to cross-link with divalent cations to form a hydrogel structure, with the goal of achieving effective drug encapsulation. Electrostatic spraying generates tiny droplets by ejecting liquid from a nozzle under a high-voltage electric field, which then form stable microspheres after cross-linking with calcium chloride. The microfluidic chip technique precisely controls fluid within micro-scale channels at the oil-water interface, generating uniform droplets that subsequently form stable microspheres upon cross-linking with calcium chloride. Gelatin is used to coat the inner layer of the microspheres, and the morphology of the microspheres produced by the two different fabrication techniques is observed using fluorescein isothiocyanate (FITC). The drug delivery performance is evaluated by biodegradation testing and the release of bovine serum albumin (BSA) through immersion of the microspheres in Hank’s Balanced Salt Solution (HBSS). After multiple experiments and tests, this study successfully fabricated two different types of microspheres using sodium alginate. The first type, solid microspheres produced by the electrostatic spray technique, exhibited a solid, non-layered structure under fluorescence microscopy, with diameters ranging from 300μm to 450μm. These microspheres had larger particle sizes and a dense structure. In degradation testing, the solid microspheres showed a weight loss rate of 79% after 72 hours, with a BSA release rate reaching 17.9% in the short term and 31% after three days. The second type, produced using the microfluidic chip technique, displayed a double-layer structure under fluorescence microscopy, with an outer layer of sodium

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