Sustained Triumvirate Delivery by Contact Lens for Post-Surgical Management

点击翻译按钮获取中文摘要

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.