口服藥物治療具容易投遞、病患接受度高、成本低廉等優點，其中，口服疏水性藥物常遭遇藥物水溶性低、吸收差、快速代謝而使生物可利用率低之困難，本研究建立一氣泡載體系統用以改善問題。此氣泡載體包含碳酸氫鈉 (SBC)、二乙烯三胺五乙酸 (DTPA)、及十二烷基硫酸鈉 (SDS) 等發泡劑，結合疏水性藥物薑黃素 (curcumin)。將此載體經口服投遞至動物腸道中，與腸液接觸後會經歷三個階段反應與結構改變: 首先，載體於接觸腸液後開始產泡，薑黃素聚集於氣泡表層SDS的疏水端，在水中形成帶有薑黃素的單層氣泡；當氣泡浮起至液面時，氣泡變為具雙層疏水層的結構，薑黃素攜載於疏水層中；氣泡接觸腸壁因表面張力改變而破裂後，親水之SDS與疏水之薑黃素形成微胞 (micelle)，微胞粒徑大小約300~ 1200 nm，便於腸道上的微皺褶細胞 (M cell) 胞吞而吸收。由TEM及IVIS結果可看出吸收的薑黃素進入淋巴系統，腸淋巴與胰臟淋巴系統可相通連，推測薑黃素因此運輸至胰臟而能在胰臟累積。為進一步探討吸收薑黃素於疾病治療之功效，我們建立大鼠急性胰臟炎動物模式，檢視其細胞激素IL-6、胰澱粉酶與組織型態隨實驗處理的變化。結果發現此氣泡載體系統能使薑黃素於腸道擴散良好，增加藥物投送表面積與形成微胞而促進吸收效率，並且具抗急性胰臟炎功效，未來期能進一步將此氣泡載體應用於其他疏水藥物輸送或以淋巴系統為標的之治療。

Oral therapeutic agents offer the advantages of greater convenience, ease of administration, and their associated complications and costs. Among all of the oral therapeutic agents, nearly half of the drug candidates have poor water solubility, and oral delivery of such drugs is limited by difficulties, including poor solubility, low permeability, instability, and rapid metabolism, all of which cause low oral bioavailability. To address these issues, we developed a bubbles carrier system which including a foaming agent (FA) —sodium bicarbonate (SBC), diethylene triamine pentaacetic acid (DTPA) dianhydride, a surfactant (sodium dodecyl sulfate, SDS) together with hydrophobic drug (curcumin). The powder mixture can self-assembly undergo 3-stage structural transformations after encountering intestinal fluid: First, the test powder produces a CO2 bubble carrier system in aqueous phase where curcumin encapsulated in the hydrophobic tail of SDS. Next, these bubble carriers gradually float to the air-water interface due to their density with structural transition of which curcumin is distributed from single layer to double layer once exposing to air. Finally, those of bubble carriers burst owing to their surface tension, and followed by a curcumin loaded missiles with a particle size range around 300~1200 nm mechanically emulsified in aqueous water. This carrier system can facilitate curcumin uptake through M-cellular endocytosis, which locate on the intestinal tract and can be visualized by CLSM. Afterward, the TEM and IVIS results suggested that those of delivered curcumin were underwent lymphocyte and then were specifically shipped into lymphatic system nearby pancreas tissue through the lymphatic drainage between intestinal and pancreas lymphatic channel. It is a niche to orally treat pancreas disease like pancreatitis. To evaluate the in vivo efficacy of this curcumin loaded carrier system via oral administration, we induced a pancreatitis rat model and elucidated their antipancreatitis ability by measuring plasma IL-6 and amylase ELISA after ingesting the test enteric coated capsule. Histological analysis of the harvested pancreas also was used in pharmacodynamics study. Our results clearly evidenced that the developed carrier system may enhance curcumin absorption and enable to significantly suppression pancreatitis via oral administration. Therefore, this carrier system is expected to apply to other hydrophobic drugs and specifically delivers hydrophobic drugs into the lymphatic system orally in the future research.

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