SBIR-STTR Award

This project intends to create a contact lens for ocular drug delivery that resolves key barriers to commercial feasibility. Contact lens drug delivery has been studied for many years, but technical challenges such as constant-rate release and controlled triggering have inhibited progress. Current prototypes release drugs at a decreasing rate, and undesirably begin releasing in storage solution (needed to keep the lens soft/wearable). A successful alternative would quickly replace topical eye drops as the treatment standard for open-angle glaucoma, which affects 2.8M Americans ($5B market) and can eventually lead to blindness. Drops have limited bioavailability (5-10% drug absorption due to burst dosage and ocular drainage) and patient compliance (20- 60% non-compliance due to tedious dosing schedule). We propose to create a silicone hydrogel contact lens with a dual-layer coating on the post-lens surface to give zero order release kinetics and protection against burst dosage failure. Also, zonal loading of drug ingredient (i.e., ring configuration) will allow targeting of specific areas active in disease. The specific aims of the Phase I proposal are: Aim 1: Novel dual-layer structure on post-lens surface to achieve near zero order drug release - We will synthesize a nanoporous polymer matrix ("1st Layer"), embed it with model drug (bimatoprost), and imprint it on the post-lens surface. We will cover this drug-loaded layer with a hydrophilic barrier coating ("2nd Layer") that provides zero-order delivery, biocompatibility and burst failure protection. Milestones: Constant-rate drug release of bimatoprost over 24-hours. Phase II goal: Extending release time to 7 days, 30 days. Animal model to evaluate release kinetics, toxicity and efficacy. Aim 2: Hydrophilic barrier coating ("2nd Layer") to control turnovr rate of post-lens tear film - Compared to ocular tear film, PLTF turnover is significantly slower, and thus advantageous to drug residence time. We will modify the post-lens surface to further stabilize the PLTF and maximize drug residence. Milestones: Produce a barrier coating on SiHy lens to reduce contact angle with simulated tear film to <15º. Phase II goal: Animal model to compare PLTF turnover rate in animal model. Aim 3: Location-specific drug loading and delivery - We will zonally load the bimatoprost into the 1st Layer using a ring configuration with inner diameter 10mm (not residing in the optical pathway) and outer diameter up to 14mm (edge of the contact lens). We hypothesize location specificity to be clinically beneficial in concentrating drug on the ocular components that are active in disease or drug treatment (e.g. trabecular meshwork/Schlemm's canal in glaucoma), and understand this aspect of zonal drug loading on the contact lens to be novel. Milestones: Majority of drug (80%) lands within well-defined area of a model cornea, minimal unwanted outflow. Phase II goal: Animal model to demonstrate efficacy correlation to specific loading locations.

Public Health Relevance Statement:


Public Health Relevance:
The proposal aims to create a commercially viable contact lens for ocular drug delivery in patients with open angle glaucoma, a disease that affects 2.8 million Americans and eventually leads to blindness. The current treatment standard of topical eye drops has notable limitations such as poor drug absorption (5-10%) and patient compliance (50% or less), while prior R&D attempts of contact lens drug delivery have failed to reach commercialization due to limitations in release duration, release rate and biocompatibility. By solving these issues, our proposed approach should supersede eye drops in drug absorption and compliance, replacing them as the treatment method of choice in the $5 billion glaucoma drug market, and creating a new platform to treat ophthalmic disease, correct vision and perform diagnostic monitoring.

NIH Spending Category:
Bioengineering; Biotechnology; Eye Disease and Disorders of Vision; Neurosciences

Project Terms:
absorption; Address; Affect; American; Animal Model; antiglaucoma drug; Area; Biological Availability; biomaterial compatibility; Blindness; Caliber; Caring; Clinical Trials; Collaborations; commercialization; Compliance behavior; Contact Lenses; controlled release; Cornea; cost; design; Devices; Diagnostic; Disease; dosage; Dose; Drainage procedure; Drops; Drug Controls; Drug Delivery Systems; drug market; Extended-Wear Contact Lenses; Eyedrops; Failure; Film; Future; Glaucoma; Goals; Healthcare; Hour; Human; Hydrogels; imprint; improved; innovation; Kinetics; Lead; lens; Location; Manufacturer Name; Marketing; Methods; Modeling; Monitor; non-compliance; novel; Open-Angle Glaucoma; ophthalmic drug; Optics; Oxygen; Pathway interactions; Patients; Performance; Permeability; Pharmaceutical Preparations; Pharmacotherapy; Phase; Polymers; prototype; public health relevance; Regimen; research and development; residence; Sales; Schedule; Self-Administered; Silicones; Specificity; standard care; Structure; Structure of sinus venosus of sclera; Surface; Taiwan; Techniques; Technology; Time; Toxic effect; Trabecular meshwork structure; transmission process; Vision; Work

Glaucoma is a major problem worldwide, with 60 million people currently affected and 112 million expected by 2040. At present, the primary treatment of glaucoma relies on medication administered as topical eye drops, with prostaglandin analogues, as the first-line therapy, representing 51% of total prescriptions. However, eye drops present significant limitations in bioavailability due to tear drainage, and a poor patient adherence rate of 50% amongst those with a daily drop regimen. Second-line drops require even more frequent dosing per day and hence worse adherence to the therapy is observed. We propose to develop a drug-delivering contact lens (DDCL) with extended wear and sustained drug release of up to 7 days for the treatment of open-angle glaucoma. The goal is to replace topical eye drops as the standard of care for glaucoma. Key advantages of the DDCL will be lower dosing frequency, direct delivery to the corneal surface at a constant rate, high-precision dosing and targeting, all by a cost-competitive lens device. The specific aims of this project are summarized as a DDCL device capable of (a) Releasing bimatoprost at a consistent rate, day and night for 7-days, (b) Achieving the highest precision in delivery dosage and target location, (c) being the best-in-class contact lens (i.e. Dk ~ 140, tear turnover cycle < 15 min., low contact angle, and easy to handle) for improving the long-term (7 days) wearing comfort, adherence, and safety. In the proposed Phase II work plan, we want to implement these improvements and evaluate efficacy using animal model studies. The proposed DDCL will not only resolve all the deficiencies of eye drop administration, but also could set a new standard against other competing technologies of ocular bandages, injectable polymers, surgical implants, etc. in the following categories: (a) The accurate control of drug release rate between first to zero order kinetics throughout the delivery duration, (b) The precise dosing of bioavailable drug amount based on matching rates of drug discharge, tear turnover and corneal adsorption, (c) The lens material innovation required for 7-day wearing comfort, safety, easy of handling (by elderlies), and at a competitive cost. After Phase II, we plan to seek regulatory approval with an IND, human clinical trials, and an NDA.

Public Health Relevance Statement:
PROJECT NARRATIVE The proposal aims to create a commercially viable contact lens for ocular drug delivery in patients with open angle glaucoma, a disease that affects 3.3 million Americans and eventually leads to blindness. The current treatment standard of topical eye drops has notable limitations such as poor drug absorption (5-10%) and patient adherence (50% or less after 6 months), while prior R&D attempts of contact lens drug delivery have failed to reach commercialization due to limitations in release duration, release rate and biocompatibility. By solving these issues, our proposed approach should supersede eye drops in drug absorption and compliance, replacing them as the treatment method of choice in the $5 billion glaucoma drug market, and creating a new platform to treat ophthalmic disease, correct vision and perform diagnostic monitoring.

Project Terms:
absorption; Adherence; Adsorption; Affect; American; Animal Model; Animals; Bandage; base; Bioavailable; Biological Availability; biomaterial compatibility; Blindness; care providers; Categories; Clinical Trials; commercialization; Compliance behavior; Consult; Contact Lenses; Convection; Cornea; cost; cost efficient; Crystalline Lens; Data; design; Devices; Diagnostic; Diffusion; Disease; Disease Management; dosage; Dose; Drainage procedure; Drops; Drug Controls; Drug Costs; Drug Delivery Systems; Drug Kinetics; drug market; Elderly; Engineering; Ensure; Evaluation; Eye; Eyedrops; Failure; Film; Fostering; Frequencies; Geography; Glass; Glaucoma; Goals; Health; Hour; Human; Hydrophilic Contact Lenses; hydrophilicity; Implant; improved; In Vitro; in vivo; Inferior; Injectable; innovation; Kinetics; lens; Location; Manufacturer Name; Methodology; Methods; Molds; Monitor; Morphology; novel; Open-Angle Glaucoma; Operative Surgical Procedures; ophthalmic drug; Optics; Oryctolagus cuniculus; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase; Polymers; Porosity; Procedures; Property; prototype; Quality of life; Regimen; research and development; rhein; Safety; Schedule; Silicones; socioeconomics; Solubility; standard care; standard of care; Structure; Structure of sinus venosus of sclera; Study models; Surface; surfactant; Synthetic Prostaglandins; Techniques; Technology; Therapeutic; Thick; Time; Toxic effect; Trabecular meshwork structure; treatment duration; Universities; Use Effectiveness; Vision; Work