多形性膠質母細胞瘤(Glioblastoma multiforme, GBM)是大腦常見之惡性腫瘤，此原發性腦腫瘤若僅使用手術，中期存活僅有3-4個月，手術後，標準給藥包括腦內貼片(Gliadel wafer)與口服(Temozolomide)。除此之外，雖有抗血管新生因子的靜脈藥物傳輸方式，但仍無法有效穿透腦血腦屏障(Blood-brain barrier, BBB)來給予腦癌治療，然而這些策略仍有不足，無法提升整體病患的存活期，且病人術後副作用多，如噁心、身體不適和腦膜炎等。正丁烯基苯(n-Butylidenephehalide, Bdph)已被證實可毒殺腫瘤，且對正常細胞毒性低，目前已用在臨床二期試驗，然而目前給藥策略主要是顱內給藥，仍需想出術後的輔助療法，以避免二次開腦的不便議題是給藥策略須改善的課題。因此跨血腦屏障方法對於腫瘤和腫瘤微環境的治療至關重要。鼻遞給藥是繞過血腦屏障的選擇之一，因鼻遞有更高的生物利用度，減少藥物全身不良反應和降低給藥劑量。本實驗設計鼻滴水膠來黏附在鼻膜上，將帶有微脂體包覆的正丁烯基苯保留在鼻腔中，減少其流失到腸胃道，並延長藥物在鼻腔滯留時間。
本研究選用感溫高分子Pluronic F127並利用化學性質來進行尾端基改質，再分別採用了1H NMR、FTIR和EA鑑定。確認其尾端基成功接枝功能性官能基後，測定其臨界微胞濃度。結果證實改質後高分子臨界微胞濃度數值均降低，使奈米微胞在體液中穩定性越好。改質後尾端基可以改善Pluronic F127容易被體液滲入而被清除的缺點，流變測試證明了改質後高分子增強了黏度從1400 Pa.s提升到1700 Pa.s以上，且其成膠溫度從33 ℃下降到24 ℃，更與臨界微胞濃度相互呼應，意味著改質後的水膠更可以有效地增加鼻腔留滯量。
動物鼻遞實驗也證明了水膠能黏附在鼻腔中，而尾端羧酸基高分子更能穿透鼻腔上皮系統來到腦部，因此改質後Pluronic F127能達成有效且非侵入式的藥物傳遞於腦癌治療。

Glioblastoma multiforme (GBM) presented as one of the most lethal malignancy and the most common adult malignant primary brain tumor. The median survival time for someone with GBM treated with surgical is around 3-4 months. After major surgical resection, the following-up traditional treatments such as implantable Gliadel wafer or oral Temozolomide drug may slightly increase the median survival time for patients. However, there are still existed some drawbacks in these treatments. For example, the low bioavailability of oral drugs and implantable drug requiring second surgery procedures. In addition, intravenous injection with anti-VEGF antibody provide the second way to treat the GBM patients, but they still exist some limitation. The high dose of intravenous injection brings the major side effect to patients. And moreover, tradition oral and intravenous drug delivery in GBM treatments methods are not the efficient way to achieve the blood-brain barrier (BBB) much less penetrate the BBB. Bdph, developed from TZU hospital, has been applied to clinical trial phase II. The advantages of Bdph are safe and shown therapeutic efficiency for patients. However, the brain surgery is required for that current clinical used wafer type bdph drug applied to patients. To cross blood-brain barrier method and low invasive administration route are also critical for reaching efficiently therapeutic effect to the brain tumor and tumor microenvironment. Intranasal drug delivery is one of the promising candidate’s route to bypass the blood-brain barrier. Moreover, the nasal delivery usually has higher bioavailability, reducing systemic adverse drug effects and lowering the dosage. This work designs the mucoadhesive hydrogel to adhere on the nasal mucous membrane that can increase the retention time of anti-brain cancer drug, Bdph, loaded liposome in the nasal cavity and reduce unnecessary loss of drug to the gastrointestinal tract. We consider to modified the terminal end of thermal sensitive Pluronic F127 to change its physical and chemical properties. The modified terminal end has possibility to increase the hydrogen bonding between the Pluronic micelles at body temperature and solve the dissolution problem of pristine Pluronic. The FT-IR, NMR, and EA were used to characterize the function grafting content and efficiency. The CMC value in the hydrogel with terminal modification was less than that of naïve hydrogel group. The rheological test showed that the modified polymer enhances the viscosity of thermal sensitive gel from 1400 Pa.s to 1700 Pa.s at body temperature and also change the gelation temperature from 33 ℃ decrease to 24 ℃. The animal nasal delivery experiment also demonstrates that the hydrogel can adhere to the nasal cavity, furthermore, the terminal carboxylate polymer even can penetrate the nasal epithelium layer to the brain. Consequently, modified Pluronic F127 achieves the efficiency, and non-invasive approach to deliver the drug and treatment.

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