Steroid-Eluting Contact Lenses for Corneal and Intraocular Inflammation

Lokendrakumar C. Bengani, H. Kobashi, A. Ross, H. Zhai, Borja Salvador-Culla, Rekha Tulsan, P. Kolovou, S. Mittal, S. Chauhan, D. Kohane, J. Ciolino
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引用次数: 35

Abstract

Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery.
类固醇洗脱隐形眼镜治疗角膜和眼内炎症
眼部炎症是世界范围内失明的主要原因之一,外用眼液(如地塞米松滴眼液)中的类固醇是治疗眼部炎症的主要方法。对于许多非传染性眼部炎症,如葡萄膜炎,每小时滴一次眼药水。高频率的给药加上眼药水的副作用导致患者依从性差。长期以来,药物洗脱隐形眼镜一直被视为持续眼部药物输送的潜在优越选择;但是在隐形眼镜中注入足够的药物并控制药物的释放仍然是一个挑战。一种地塞米松释放型隐形眼镜(Dex-Lens)以前是通过将地塞米松聚合物薄膜封装在水凝胶型隐形眼镜的外围而开发出来的。在这里,我们在兔模型中证明了Dex-Lens治疗眼前炎症的安全性和有效性。Dex-Lens给药7天(兔模型)。在Dex-Lens提取物的眼部刺激研究(Draize试验)中,正常兔眼未观察到不良事件。Dex-Lenses有效抑制缝合线诱导的角膜新生血管和炎症7天,脂多糖诱导的前葡萄膜炎5天。Dex-Lenses的疗效与每小时给药的地塞米松滴眼液相似。在角膜新生血管研究中,与佩戴Dex-Lens的兔眼相比,未接受治疗的兔眼和佩戴载体性晶状体的兔眼观察到明显的角膜水肿。在这些研究中,dex - lens耐受性良好,没有表现出毒性迹象。地塞米松洗脱隐形眼镜可能是治疗眼部炎症的一种选择,也是眼部药物输送的一个平台。
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