小腸上皮細胞(epithelial cell)主要是由細胞內的酵素與連接細胞之間的蛋白質錯合物構成。而由於細胞膜主要是由脂雙層所構成，因此親脂性分子可以直接藉由細胞膜(transcellular pathway)通過上皮細胞；反之，親水性分子無法直接穿過疏水性的細胞膜，需要經由細胞與細胞之間的空隙(paracellular pathway)通過上皮細胞。位於上皮細胞之間的蛋白質錯合物tight junction可以選擇性地讓一些親水性分子進出上皮細胞。許多具有相當療效的口服親水性藥物如蛋白質藥物和胜肽類藥物等，除了會遭受到胃酸的破壞外，同時也無法順利通過小腸上皮細胞膜的疏水性脂雙層結構，進而影響腸道的藥物吸收。
在本實驗室先前的研究成果中，已成功利用幾丁聚醣與聚麩氨酸，製備奈米微粒載體以包覆胰島素，作為口服藥物釋放系統，由於此奈米微粒其pH值的穩定範圍為pH 2.5 ~ pH 6.6。因此本研究目的主希望藉由三甲基幾丁聚醣Trimethyl Chitosan（簡稱TMC），增加奈米微粒於pH值的穩定範圍程度，進而提高口服藥物奈米微粒載體的生體可用率。
本研究主要分為三部分。第一部分為合成不同接枝度TMC，並分別利用高磁場核磁共振儀(NMR)鑑定TMC的接枝度。第二部份為選擇不同接枝度TMC與γ-PGA製備奈米微粒，觀察奈米微粒在不同pH值下之粒徑變化和電荷性差異，以探討TMC和γ-PGA的奈米微粒在不同pH值下穩定性分析，選擇最佳的接枝度條件以進行後續藥物包覆。
第三部分則是以Caco-2 cell monolayers作為體外實驗的model，發現TMC/γ-PGA的奈米微粒具有打開Caco-2 cell monolayers細胞間tight junction的能力。藉由量測細胞下層medium發現胰島素的確可經過parecellular pathway而通過Caco-2 cell monolayers，並進一步利用(CLSM)共軛焦雷射掃描顯微鏡證明與胰島素的確可進入細胞內。最後模擬口服途徑的pH值變化進行藥物釋放，進一步證明TMC/ γ-PGA所製備的奈米微粒的確可解決Chitosan/γ-PGA在中性環境下藥物過度釋放的問題。

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