乾眼症 (Dry eye disease, DED) 是眼表的多因素疾病，其特徵在於淚膜穩定
狀態失衡，並伴隨著眼部症狀。其中，淚膜過滲和不穩定性、眼表的發炎和損傷
以及神經感覺異常是致病的因素。近年來，由於 3C 產品的進步以及高依賴性，
乾眼症成為了高度普及的疾病。除此之外，治療眼科疾病 (如：青光眼及眼內炎
等等) 的眼藥水中，常添加苯扎氯銨 (Benzalkonium chloride, BAK) 作為防腐劑，
此成分也會導致乾眼及發炎情況的產生。阿魏酸 (Ferulic acid, FA) 具有良好的
抗氧化能力及抑制發炎的作用，然而使用傳統的眼藥水滴劑停留於眼表的時間短
暫且生物可利用低。在本研究中，將阿魏酸接枝於幾丁聚醣 (Chitosan, Cs) 上並
製備出奈米粒子，再進一步結合羧甲基纖維素 (Sodium carboxymethyl cellulose,
CMC) 發展出可注射式水膠，期望能延長藥物於眼表停留的時間並降低給藥頻率，
以達到更好的治療效果。研究中結果顯示未載藥的奈米粒子大小平均為 157.1 ±
8.19 nm，粒徑分布 PDI 為 0.409 ± 0.014，表面電位為 31.4 ± 0.81 mV。而搭載
阿魏酸的載藥奈米粒子大小平均為 183.6 ± 2.91 nm，粒徑分布 PDI 為 0.311 ±
0.005，表面電位為 28.1 ± 0.87 mV ，另以苯扎氯銨誘發角膜上皮細胞的損傷來
模擬乾眼症的發炎情況，後續定量即時聚合酶連鎖反應及細胞存活率來評估阿魏
酸接枝幾丁聚醣奈米粒子對受損細胞的可能療效。根據上列實驗結果，阿魏酸接
枝幾丁聚醣奈米粒子結合可注射水膠有應用於乾眼症治療的潛力。

Dry eye disease (DED) is a multifactorial disease of the ocular surface, which is
characterized by an imbalance in the stable state of the tear film, accompanied by ocular
symptoms. Among them, tear film hyperosmosis and instability, ocular surface
inflammation and damage, and neurosensory abnormalities are the pathogenic factors.
In recent years, due to the progress and the high dependence of electronic products, dry
eye disease has become a prevalent disease. Besides, the eye drops for the treatment of
ocular diseases (such as glaucoma and endophthalmitis) often added benzalkonium
chloride (BAK) as a preservative. This ingredient can also cause dry eye and the
inflammation of ocular surface. Ferulic acid (FA) has good anti-oxidation and anti-
inflammatory effects. However, traditional eye drops have a short ocular residence time
and low bioavailability. In this study, ferulic acid was grafted on chitosan (Cs) to
prepare nanoparticles and combined with carboxymethyl cellulose (CMC) to develop
an injectable hydrogel expected to prolong the short ocular residence time and reduce
the frequency of administration, hoping to improve therapeutic effects. The mean
particle size of blank nanoparticles and FA-loaded nanoparticles was 157.1 ± 8.19 and
183.6 ± 2.91 nm with positive zeta potential 31.4 ± 0.81 and 28.1 ± 0.87 mV. In addition,
BAK-induced damage to corneal epithelial cells was used to simulate the inflammation
of DED. The quantitative real-time polymerase chain reaction and cell viability assay
were used to evaluate the effects of FA grafted Cs nanoparticles on damaged cells.
According to the experimental results, FA grafted Cs nanoparticles combined with
injectable hydrogel has the potential to be used in the treatment of DED.

65

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