Sustained Triumvirate Delivery by Contact Lens for Post-Surgical Management

白内障手术已经成为一种非常常见的手术，每年全球约有1000万例白内障手术1 由于人口老龄化，预计将大幅增加。手术可能会导致严重的炎症。 它是通过滴眼液来提供抗生素、类固醇和非甾体抗炎药来管理的，但这种方法有很多 问题包括生物利用度低3和50%的遵从性。4事实上，在几乎93%的情况下，专利使用不正确 使用眼药水的技巧5。这些缺陷推动了对开发缓释装置的研究 地塞米松，如DEXYCUTM和DEXTENZA®。虽然这些药物提供了好处，但也没有提供所有的药物，所以 患者可能仍然需要滴注抗生素眼药水，以将感染的可能性降至最低。我们会解决这个问题的 问题是，设计的隐形眼镜可以以受控的速度提供所有三种药物，延长持续时间 生物利用度使其显著优于基于滴剂的疗法以及其他商业设备。此外 对于后发性白内障，我们的方法将适用于任何手术后的治疗，包括屈光性角膜切削术 (PRK)，这已经包括在手术后放置绷带镜片。隐形眼镜比滴眼液有很多优点 包括缓释，通过用1-4个或更高的镜片取代约100滴药水来提高依从性 生物利用度，将导致更一致的浓度在眼组织，从而改善治疗。我们有 开发了一种新的专利方法，通过在商业中加入维生素E(一种生育酚)来延长递送时间 硅胶水凝胶隐形眼镜。使用已经获得FDA批准的商用隐形眼镜，减少了障碍 为了翻译。我们的方法也是创新的，因为可以很容易地通过简单的 先在维生素E和乙醇溶液中浸泡，然后在去离子水中浸泡。我们之前相当可观的结果是 结果表明，我们的方法延长了多种眼科药物的药物释放时间，这对该项目至关重要 同时保持隐形眼镜的所有关键性能，包括透明度、润湿性、紫外线阻挡和氧气 渗透性。具体地说，我们显示在ACUVUE OASYS中加入30%(w/w)干基维生素E 隐形眼镜将左氧氟沙星的释放期延长至3天，将地塞米松和酮咯酸的释放期延长至7天。这项研究 目的制造和表征AIM-1中的晶状体，并在AIM中测试新西兰白兔的药代动力学 2.该方法将对NB-CL的持续给药和疗效提供见解，并导致一种新的装置 持续的术后管理。我们的方法承诺提高依从性并将药物用量降至最低 为了改善治疗而进行的变化。在完成此处建议的第一阶段研究后，我们将提交IND启用阶段 2.新西兰大白兔手术模型的有效性验证方案。

Cataract surgery has become a very common procedure with about 10 million cataract operations each year in the world1 with a significant increase expected due to aging of the population. The surgery could result in significant inflammation which is managed by instillation of eye drops to deliver antibiotics, steroids and NSAID but this approach has many problems including low bioavailability3 and <50% compliance.4 In fact, in almost 93% cases, patents use incorrect technique to administer the eyedrops5. These deficiencies have driven research in developing devices for sustained release of dexamethasone such as DEXYCUTM and DEXTENZA®. While these offer benefits, neither deliver all drugs and so patients may still require instillation of antibiotic eye drops to minimize the possibility of infections. We will solve this problem by designing contact lenses that can deliver all three drugs at controlled rates for extended durations with high bioavailability making this significantly superior to the drop-based therapy as well as other commercial devices. In addition to post cataract, our approach will be usable for any post-surgical management including Photo refractive keratectomy (PRK) which already involves placing a bandage lens after surgery. Contacts lenses offer many advantages over eye drops including sustained release that will improve compliance by replacing about 100 drops with 1-4 lenses and higher bioavailability that will lead to more consistent concentrations in ocular tissues resulting in improved therapy. We have developed a novel, patented approach for extended delivery by incorporation of vitamin E (a tocopherol) in commercial silicone hydrogel contact lenses. Use of commercial contact lenses that are already approved by the FDA, reduces barriers to translation. Our approach is also innovative because of the ease with which the barriers can be incorporated via simple soaking steps first in a solution of vitamin E and ethanol, followed by in DI water. Our considerable prior results have shown that our approach increases the drug release duration of multiple ophthalmic drugs which is critical to this project while maintaining all key properties of the contact lenses including transparency, wettability, UV-blocking, and oxygen permeability. Specifically, we showed that incorporation of 30% (w/w) on dry basis of vitamin E in ACUVUE OASYS lenses increases the release duration of levofloxacin to 3 days and dexamethasone and ketorolac to >7 days. This research aims to manufacture and characterize the lenses in Aim 1 and test pharmacokinetics in New Zealand white rabbits in Aim 2. The approach will provide insights into sustained drug delivery and efficacy with NB-CL, and lead to a novel device for post-surgical management in a sustained manner. Our approach promises to improve compliance and minimize drug variations to improve therapy. After completion of Phase 1 studies proposed here, we will submit an IND enabling Phase 2 proposal focusing on proving efficacy in a surgical model of New Zealand White rabbit model.