口服藥物為最常見的給藥方式，優點在於口服藥物所帶來的方便性且可減少患者對注射給藥方式所帶來的畏懼。在口服親水性藥物如蛋白質藥物和胜肽類藥物過程中，藥物除了會遭遇胃酸與酵素的破壞外，更由於小腸上皮細胞(epithelia cell)的疏水性脂雙層結構，造成影響腸道的藥物吸收。本研究乃為研發一胰島素奈米微粒載體系統，經冷凍乾燥後，置於一塗佈有腸衣之膠囊中，做為口服劑型。實驗上分3部份來進行。第一部分為混合trehalose與chitosan(CS)/ γ-poly-glutamic-acid(γ-PGA)奈米微粒後再經冷凍乾燥後所形成的粉末態奈米微粒，經由TEM觀察奈米微粒型態及利用粒徑分析儀分析奈米微粒的酸鹼敏感性質來証實冷凍乾燥並不影響其基本性質。第二部分將粉末狀態的奈米微粒填充於膠囊，利用dip coating的方式將L100-55製成腸衣塗佈於膠囊外，進行模擬體外腸胃道環境測試，藉由HPLC量測藥物釋放量得知經腸衣保護後確實可避免藥物在胃中損失。同時以Caco-2 單層細胞作為體外實驗模型，經由量測transepithelial electrical resistance (TEER) 後，發現粉末態CS/γ-PGA奈米微粒確實具有可逆性調控tight junction的能力；同時藉由量測transwell下層溶液分析胰島素含量，證實胰島素確實可經由paracellular pathway 通過Caco-2 細胞單層，並計算出於pH 6.6時Papp為3.34×10-6 cm/s。第三部分是動物實驗，將已包覆藥物的奈米微粒置於膠囊後，外層塗佈不同種類的高分子腸衣來進行動物實驗，實驗後發現經Eudragit® L100-55包覆的膠囊其血糖值下降至原本的53%；而Eudragit® S100則下降至72%。更由不同時間下取出老鼠尾巴血液，以bovine insulin kit量測糖尿病老鼠血漿中的bovine insulin濃度並計算出其生體可用率為20.1± 0.3%。以上的實驗結果顯示，本研究所研發的奈米微粒膠囊系統可以用來做為口服胰島素的新劑型。

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