SBIR-STTR Award

This Small Business Innovation Research Phase I project assesses the feasibility of using a novel synergistic drug-polymer ocular film product based on a modified biopolymer hydrogel to deliver antibiotics directly, locally and continuously to the ocular surface over an extended weekly period. This film combines the pro-healing, anti-inflammatory effects hyaluronic acid with slow release of an ophthalmic antibiotic. Topical ocular antibiotics require frequent dosing (i.e., hourly for corneal ulcers), often resulting in improper administration, causing suboptimal bioavailability to the eye and considerable waste. This novel polymer film can be placed on the ocular surface topically to deliver a well-known ophthalmic antibiotic. We propose to expand on known benefits of topical hydrogels by delivering antibiotics to reduce bacterial infections locally while simultaneously accelerating and improving healing. Prototype films of hydrogel containing antibiotics will be produced and evaluated for film degradation, anti-bacterial efficacy, and drug release. Safety and tolerability of the antibiotic-containing films will be demonstrated in a preclinical rabbit model. We anticipate being able to produce a well-tolerated antibiotic-releasing film product prototype and demonstrate the desired characteristics. Such a film would allow us to progress to a Phase II SBIR to optimize a sterile and clinically useful commercial product.


The broader impact/commercial potential of this project is development of a new ocular drug delivery product that will improve patient care by providing a more efficient, effective, convenient, and consistent means of antibiotic delivery directly to the ocular surface. Using a known polymer carrier with intrinsic healing properties, this product will deliver continuous adequate doses locally, thus eliminating the frequent topical (up to every hour) and/or systemic doses of antibiotics for a wide range of infectious ophthalmic conditions. This improves patient compliance and patient outcomes, while reducing health care costs. Relevant eye diseases include active infections of the cornea and conjunctiva, as well as prevention of potential infections associated with various ocular surgeries and diseases. This topical extended release product addresses important unmet medical needs in the military and in civilian populations by providing healthcare provider-placed antibiotic product administered acutely. The antibiotic-containing films produced and evaluated in Phase I can ultimately lead to the development of a commercially viable ocular care product to address these unmet needs. Further, by demonstrating release of polybasic antibiotics, such a system could be expanded to deliver other antimicrobials to treat ophthalmic fungal or viral infections, which represent significant challenges in developing countries.

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will be to more effectively treat serious, infectious corneal ulcers by delivering antibiotics directly to the eye?s surface via a novel, biodegradable flexible polymer film. The platform will deliver drug continuously, thereby eliminating the need for hourly eye drops. This product can be administered immediately, at time of injury, allowing health professionals to ensure best treatment and outcomes. The platform solves immediate unmet medical needs in corneal infections, which are a result of improper contact lens wear, as well as increased incidence of eye trauma in the US military. Worldwide, corneal ulcers commonly result in blindness due to difficulty in obtaining and applying medication. These antibiotic-containing films ? which combine polymer science, chemical bioengineering, and drug pharmaceutical formulation innovation ? will bring improved commercially available solutions to vision-threatening conditions far beyond corneal ulcers by employing this novel platform, which provides an effective, easy-to-administer, broad application of sustained, local ophthalmic drug delivery. Broader societal impact lies in the scientific and technical discoveries and innovation, as well as the ability to educate/train others on advances in polymer drug delivery science. The proposed product is based on a proprietary, cross-linked hyaluronic acid (HA) polymer technology, formulated with antibiotics to deliver drug locally and continuously to the ocular surface over multiple days. The well established healing effects of HA, combined with continual-release antibiotics create a novel product that fulfills a significant unmet medical need. Current topical ocular antibiotics require round-the-clock dosing. In addition to being inconvenient, if administered incorrectly, today?s eye drops can lead to continued eye trauma/damage, less-than-optimum outcomes, and considerable waste. The cross-linked, ?tunable? film ? applied by a medical professional ? contains a commercially proven antibiotic that is released over multiple days in precise quantities to the ocular surface with no further patient self-dosing required. In the grant?s Phase I, prototype HA films containing antibiotics were produced, sterilized, and successfully tested in vitro and in vivo for drug release and tolerability. Phase II will include shape development, formulation/drug-release optimization, drug content release confirmation in vivo, and development of a reliable manufacturing process for sterile shelf-stable films. The objective of this Phase II proposal is to continue to optimize and develop sterile antibiotic-releasing cross-linked HA films to be applied locally to the ocular surface to treat sight-threatening corneal ulcers.