Sustained Triumvirate Delivery by Contact Lens for Post-Surgical Management

通过隐形眼镜进行持续三效治疗以进行术后管理

• 批准号: 10383014
• 负责人: Chris Adams
• 金额: $ 30.55万
• 依托单位: DIOPTER TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10383014
• 关键词: Aging; Anti-Inflammatory Agents; Antibiotics; Aqueous Humor; Bandage; Biological Availability; Cataract; Cataract Extraction; Chronic; Contact Lenses; Devices; Dexamethasone; Disease; Dose; Drops; Drug Delivery Systems; Drug Kinetics; Endophthalmitis; Ethanol; Eyedrops; FDA approved; Fibrin; Frequencies; Goals; Hydrogels; In Vitro; Infection; Inflammation; Ketorolac; Lead; Left; Legal patent; Levaquin; Measures; Modeling; Moxifloxacin; New Zealand; Non-Steroidal Anti-Inflammatory Agents; Operative Surgical Procedures; Oryctolagus cuniculus; Oxygen; Patients; Permeability; Pharmaceutical Preparations; Phase; Physiologic Intraocular Pressure; Population; Problem Solving; Procedures; Property; Publications; Research; Risk; Shapes; Silicones; Sterilization; Steroids; Surgical Management; Surgical Models; Techniques; Testing; Therapeutic; Tissues; Uveitis; Variant; Vitamin E; Water; Wettability; alpha Tocopherol; base; commercialization; design; drug efficacy; drug testing; improved; in vivo; innovation; insight; lens; macula; mathematical model; novel; operation; ophthalmic drug; phase 1 study; safety testing; sodium phosphate; translational barrier

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.

白内障手术已成为一个非常普遍的程序，每个世界都有1000万个白内障手术！ 由于人群的老化，预期的大幅增加。 通过滴注眼滴以提供抗生素，类固醇和NSAID来管理，但这种方法有很多 包括低生物利用度3和<50％合规性在内的问题。4实际上，在几乎93％的情况下，专利使用不正确 管理EyeDrops5的技术。 诸如Dexycutm和Dextenza®等地塞米松。 患者可能需要滴注抗生素眼滴以最大程度地减少感染的可能性。 通过设计隐形眼镜，可以在延长持续时间内以受控速率传递所有三种药物，高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高高！ 生物利用度使基于下降的疗法以及其他商业设备都显着优越。 tost白内障，我们的方法将用于任何后手术后的管理，包括照片折射术切除术 （PRK）已经涉及在手术后放置绷带镜头。 包含持续的释放，而大约有100滴，带有1-4个镜头，更高 生物利用度将导致眼组织中更多的巩固，从而改善了治疗。 通过将维生素E（A生育酚）掺入商业 硅水凝胶隐形眼镜的使用。 翻译我们的方法也是创新的元素，因为可以通过简单的 首先在维生素末端乙醇的溶液中浸泡步骤，然后在DI水中浸泡。 表明我们的方法增加了多种眼科药物的药物释放持续时间，这对这个项目至关重要 同时保持隐形眼镜的所有关键特性，包括透明度，润湿性，紫外线阻滞和氧气 渗透性。 镜片将左氧甲酸的释放持续时间增加到3天，地塞米松和Ketorolac持续到> 7天 旨在在AIM 1中制造和表征镜头，并在新西兰白兔子中测试药代动力学 2。该方法将提供有关NB-CL持续药物递送和功效的见解，并导致一种新颖的设备 术后管理以一种持续的方式。 改善治疗的变化。 2提案重点是在新西兰白兔模型的外科手术模型中证明功效。