心肌梗塞 (Myocardial infarction) 是一種急性且嚴重的心臟疾病，原因在於冠狀動脈阻塞使氧氣和養分無法輸送到心肌細胞，將導致心臟組織永久受損壞死。經治療後血液會重新流至缺血的細胞，但再灌注治療後的氧化壓力會誘使發炎因子產生，使得心肌受損。因此，針對缺血再灌注損傷的預防及治療成為心肌梗塞治療中不可忽視的存在。現今的治療方式包含再灌注前的預處理及再灌注後的治療，如缺血預處理、基因或細胞策略以及藥物治療等。然而，預處理的前置準備時間較長可能耽誤治療，基因或細胞策略是仍在實驗室內的研究，藥物投遞則有生物利用度低的問題。
N-乙醯半胱胺酸 (N-acetylcysteine, NAC) 的抗氧化能力一直備受矚目，同時作為穀胱甘肽 (Glutathione, GSH) 的前驅物，NAC 可以補充 GSH 在體內的濃度，增強人體的解毒能力；而泊洛沙姆 (Pluronic F127, PF127) 為一種兩親性的高分子材料，大量研究證實 PF127 具有極佳的生物相容性且為良好的藥物載體。在本研究中製備同時具備溫敏性以及氧化應答能力的苯硼酸酯泊洛沙姆共聚雙響應水凝膠 (PBAP-PF127) 並載入藥物，雙響應水膠能透過注射到達人體內，在體溫下凝膠，並於氧化壓力的疾病環境下，緩慢且持續釋放藥物以達到更好的治療效果。
本研究以 4-(Hydroxymethyl)phenylboronic acid pinacol ester (PBAP)、1,1'-Carbonyldiimidazole 及 PF127 製備 PBAP-PF127 高分子材料，利用傅立葉轉換紅外光譜、核磁共振與熱重分析儀分析材料改質前後的特徵峰及熱裂解溫度變化，將高分子配製成 20 wt% 水膠後，進一步評估雙響應水膠的性質，包含凝膠溫度、水膠形貌、溶脹與降解特性及對細胞的安全性，如水膠萃取液之毒性、滲透壓，確認水膠適用性後載入 NAC，評估藥物緩釋的效果。
後續以過氧化氫 (Hydrogen peroxide) 誘導 H9c2 大鼠心肌細胞產生氧化壓力損傷，並加入載有藥物之 PBAP-PF127 水膠進行療效評估，結果顯示雙響應水凝膠能降低細胞凋亡程度與發炎因子，進一步提升 H9c2 的存活率。
綜上所述，本研究開發之 PBAP-PF127 水膠應用於心血管疾病的治療應具一定的潛力。

Myocardial infarction is an acute and severe heart disease caused by blockage of the coronary arteries that prevents oxygen and nutrients from being delivered to the myocardial cells, resulting in permanent damage to the heart tissue and death. After treatment, blood will flow back to the ischemic cells, but oxidative stress after reperfusion therapy can produce inflammatory factors that can damage the myocardium. Therefore, the prevention and treatment of ischemia-reperfusion injury have become integral to myocardial infarction treatment. Current treatment modalities include pre-treatment before reperfusion and post-reperfusion therapy, such as ischemic preconditioning, genetic or cellular strategies, and pharmacological therapy. However, pretreatment has a long lead time and may delay treatment, genetic and cellular strategies are still in the laboratory, and drug delivery has a low bioavailability problem.
N-acetylcysteine (NAC) has been noted for its antioxidant capacity. As a precursor of glutathione (GSH), NAC can replenish the concentration of GSH in the body and enhance the detoxification ability of the body. Pluronic F127 (PF127) is an amphiphilic polymer, and numerous studies have demonstrated that PF127 has biocompatibility and can be a drug carrier. In this study, a dual-response hydrogel (PBAP-PF127) with both temperature-sensitive and oxidative response capabilities was prepared and loaded with the drugs. The dual-response hydrogel can be injected into the body, gel at body temperature, and slowly and continuously release the drugs under oxidative stress conditions to achieve better therapeutic effects.
In this study, PBAP-PF127 polymers were prepared by 4-(hydroxymethyl)phenylboronic acid pinacol ester (PBAP), 1,1'-carbonyldiimidazole and PF127, and the characteristic peaks and thermal decomposition temperature changes were analyzed by Fourier-transform infrared spectroscopy, nuclear magnetic resonance, and thermogravimetric analysis. After the polymer was prepared into 20 wt% hydrogels, the properties of the dual-response hydrogel were further evaluated, including gelation temperature, hydrogel morphology, swelling and degradation characteristics, safety to cells, such as toxicity and osmolality of the hydrogel extract. After confirming the suitability of the hydrogel, NAC was loaded into the hydrogel to evaluate the in-vitro drug release profile.
Subsequently, oxidative stress damage was induced by hydrogen peroxide in H9c2 rat cardiomyocytes, and the efficacy was evaluated by adding PBAP-PF127 hydrogel loaded with the drug. The results showed that the dual-response hydrogel reduced apoptosis and inflammatory factors in the oxidative environment, further enhancing the survival rate of H9c2.
In summary, the PBAP-PF127 hydrogel developed in this study should have potential application in the treatment of cardiovascular diseases.

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