青光眼 (Glaucoma) 是由一種視神經病變所引發的眼部疾病，眼部壓力過高是主要成因之一，較高的眼壓會造成視神經的受損，進而造成患者視力減弱甚至失明，目前臨床治療多使用局部眼藥水滴點的方式來控制患者眼壓，然而，由於此治療方式生物利用度過低且需要頻繁的給藥，尚有許多限制需要克服。近年來研究顯示含一氧化氮藥物可透過引起小樑網狀組織 (Trabecular meshwork, TM) 的鬆弛，增加常規房水引流來調節眼內壓，還可以調節細胞凋亡及發炎反應，針對氧化壓力的損傷進行治療。羥丙基甲基纖維素 (Hydroxypropyl methylcellulose, HPMC) 是一種具黏彈性及黏膜貼附性的高分子，並且被美國食品藥物管理局核准用於眼科滴劑或口服藥物的非活性成分，它可以通過延長藥物與角膜的接觸時間，顯著改善眼部病變的治療。本研究發展一藥物載體，預期能設計出長效且穩定的青光眼給藥系統。在研究中以聚乳酸-甘醇酸 (Poly (Lactide-co-Glycolide), PLGA) 製備出奈米粒子 (Nanoparticles, NPs) 並包覆亞硝基穀胱甘肽 (S-nitrosoglutathione, GSNO) ，再搭配以甲基丙烯酸酐 (Methacrylic anhydride, MA) 改質後具黏膜貼附特性的羥丙基甲基纖維素水凝膠，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。 除了進一步評估奈米粒子的形態、粒徑、粒徑分布及界達電位 (Zeta potential)，也進行過氧化氫清除能力、藥物釋放實驗等研究。水凝膠方面則利用傅立葉轉換紅外光譜與核磁共振光譜分析材料改質前後的特徵峰及化學結構變化，並進行流變性質測試及體外生物相容性實驗。

實驗結果顯示改質後的HPMC具有良好的生物相容性，流變測試也顯示改質後的水膠有更好的黏膜貼附特性。在載藥濃度的選擇上，從細胞存活率的結果顯示， GSNO奈米粒子 (GSNO-NPs) 對TM細胞的安全濃度約為80 μM。將 GSNO-NPs以不同濃度分別與TM細胞進行共培養，發現低濃度的GSNO-NPs具有促進TM細胞增殖特性。

Glaucoma is a kind of eye disease caused by optic neuropathy. Elevated intraocular pressure (IOP) is one of the main causes, which can cause damage to the optic nerve, and can lead to impaired vision and even blindness in patients. At present, topical eye drops are the most common way to control the IOP of patients. However, there are still many limitations that need to be overcome due to the low bioavailability of the drug and the need for frequent administration. Recent studies have shown that drugs containing nitric oxide can increase conventional aqueous humor drainage to regulate intraocular pressure by relaxing trabecular meshwork (TM). It can also regulate cell apoptosis and inflammation, and target oxidative stress-induced damage.

Hydroxypropyl methylcellulose (HPMC) is a viscoelastic polymer and is approved by the US Food and Drug Administration as an inactive ingredient for ophthalmic drops or oral medications. It possesses mucoadhesive ability which significantly improves the treatment of eye diseases by prolonging the contact time between the drug and the cornea.

This research develops a drug carrier, which is expected to provide a sustainable and stable drug delivery system for glaucoma. Poly (Lactide-co-Glycolide) (PLGA) was used to prepare nanoparticles (NPs) loaded with S-nitrosoglutathione (GSNO)，and mixed with HPMC modified by methacrylic anhydride (MA) which has shown improved mucoadhesion characteristics, to prolong the retention of the drug on the ocular surface and reduce the frequency of administration to achieve better treatment effect. In addition, we evaluated the morphology, particle size, particle size distribution and zeta potential of the nanoparticles. Hydrogen peroxide scavenging activity and in vitro drug release were also tested. Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy were used to analyze the characteristic peaks and chemical structure of the modified hydrogels, rheology and biocompatibility test of materials were also carried out.

The experiment results show that the modified HPMC hydrogels have good biocompatibility and better mucoadhesion characteristics. The cell viability test shows that the safety concentration of GSNO-loaded NPs (GSNO-NPs) for TM cells is about 80 μM. GSNO-NPs were co-cultured with TM cells at different concentrations, and it was found that low-concentration GSNO-NPs promotes the proliferation of TM cells.

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