Development of an eluting-supramolecular assembled contact lens-like device for the topical biogenic treatment of cataracts

Abstract

This project tackles two main issues: poor ophthalmic drug bioavailability and treatment alternatives for cataract. A synergistic approach of developing a bi-composite drug delivery system with components possessing the capacity to improve drug solubility, drug stability, residence time, amount of drug available at the membrane surface and membrane permeability was developed through the application of highly potent nanosponges and an in situ gelling system. The newly synthesized bi-composite system was assessed for toxicity using the Epiocular Tissue Model™ and was found to be non-toxic with a Draize score of 18.15. It was then assessed for potential to deliver bioactives in vivo using 2-2.5kg New Zealand White Rabbits. Two main administration routes were tested; the topical and intravitreal route. Assays for detection of the bioactives from the aqueous humor, lens and vitreous humor were performed and quantitative analysis was performed using Ultra Performance Chromatography (UPLC). The bioactive levels reached up to 80% saturation in some ocular tissue sites. The next step involved a second in vivo study where cataract was induced on 4-5 weeks New Zealand White pups using diquat dibromide. Following confirmation of cataract development by slit lamp illumination, the bi-composite drug delivery system was used as a carrier for a bioactive combination (acetyl-carnosine and nicotinamide). A single intravitreal injection of the bioactive bi-composite system was able to dissolve early stage cataract within minutes of administration and was able to delay onset and progression of cataract in the preventative group of the study. Although this positive effect was observed, the cataract returned in 24-48 hours, which lead to the hypothesis that continuous use or multiple administrations of the system may derail cataract onset and progression. Although signs of cataract development were observed in the preventative group, some structures such as the cornea still remained clear for prolonged periods of time (14 days) as compared to the group that was only administered the cataract-inducing agent. An alternative drug delivery approach that was assessed was the use of a contact lens-like device. The short-comings experienced such as the inability to obtain the correct shape and surface properties without the proper instrumentation, and inability to assess important properties such oxygen permeability in the absence of the instrumentation lead to its exclusion during the in vivo studies to prevent causing unnecessary harm and discomfort to animals.