以市售隱形眼鏡結合搭載貝伐單抗之奈米微粒於年齡相關性黃斑部病變治療之應用

Abstract

年齡相關性黃斑部病變是老年人口失明的主要原因之一，因此也被稱為老年性黃斑部病變。研究表明，許多細胞機制的功能障礙與它的發展進程相關，像是粒線體功能異常、活性氧物質增加、蛋白質的聚集、細胞自噬作用以及毒素清除機制受損等，最後導致視網膜受損及黃斑部病變，其中，疾病發展過程中會使血管內皮生長因子VEGF大量分泌，促使血管新生作用異常，脈絡膜微血管大量增生。 目前臨床上治療手段以抗VEGF療法為主，將抗VEGF藥物經由玻璃體內注射或結膜下注射至眼內，抑制VEGF在血管內作用，然而眼內注射有嚴重的眼部感染及視網膜剝離的風險，因此我們推測是否能透過非侵入性的策略來達到給藥目的，提供眼部治療新的方向。本研究以高分子材料作為奈米載體搭載抗血管新生藥物癌思停® (Bevacizumab)，並結合市售隱形眼鏡構成複合型藥物遞送系統，探討以簡易的配戴隱形眼鏡的方式達到給藥的可行性，改善侵入眼睛的需求。 本研究合成出平均粒徑338.8 ± 18.5 nm及214.6 ± 6.0 nm之PLGA奈米微粒及Chitosan奈米微粒，包覆率分別為54.08 %及67.25 %。於體外研究中，可維持15天左右的緩釋能力；於角膜吸附研究中，配戴一定時間後，顯示出一定比例的奈米藥物可由隱形眼鏡轉移至眼表上；於人類視網膜色素上皮細胞研究中呈現無毒性，且經過藥物溶液的浸泡不會影響隱形眼鏡透光度、視物能力；於體外血管新生分析研究中呈現抑制VEGF作用，並回復正常狀態。綜合上述結果，本研究證實了Bevacizumab奈米遞送結合市售隱形眼鏡成為脈絡膜血管增生中非侵入性治療的潛力及可行性。

Age-related macular degeneration (AMD) is a major cause of blindness among the elderly population. Extensive research has demonstrated that cellular dysfunction plays a significant role in the development of AMD, leading to retinal damage and macular degeneration. This cellular dysfunction triggers the secretion of vascular endothelial growth factor (VEGF), which in turn stimulates abnormal angiogenesis and the formation of choroidal neovascularization (CNV). Currently, the primary clinical treatment for AMD involves anti-VEGF therapy. Anti-VEGF drugs are administered via intravitreal or subconjunctival injections to inhibit the activity of VEGF. However, it is important to note that intraocular injections carry inherent risks such as eye infections and retinal detachment. To address these concerns, this study proposes a novel approach in which Avastin® (Bevacizumab), an anti-angiogenic drug, is loaded into a polymer-based controlled-release system and combined with commercially available contact lenses. The average particle sizes of the Avastin®-loaded PLGA and chitosan systems were measured as 338.8 nm and 214.6 nm, respectively. The encapsulation efficiencies were found to be 54.08% and 67.25% for the PLGA and chitosan systems, respectively. In vitro studies demonstrated sustained drug release from the PLGA and chitosan nanoparticles for approximately 15 days. Additionally, corneal adsorption capacity studies revealed that wearing contact lenses loaded with nanoparticles allowed for the deposition of a portion of the drug onto the cornea. Biocompatibility tests conducted on human retinal pigment epithelial cells (ARPE-19) showed no toxicity associated with the nanoparticles. Furthermore, soaking the contact lenses in the drug solution did not affect the light transmittance of the lenses. In vitro angiogenesis analysis demonstrated the ability of the Bevacizumab nanoparticles to inhibit VEGF and restore angiogenesis to a normal state. Based on the findings of this study, it can be concluded that Bevacizumab nanoparticles combined with commercial contact lenses hold promise as a non-invasive treatment for CNV. Further research and clinical trials are necessary to evaluate the safety, efficacy, and long-term outcomes of this combined therapy in the management of CNV associated with AMD.