Glaucoma is the leading cause of irreversible blindness in the world. Because elevated intraocular pressure(IOP) and IOP fluctuations are the primary risk factors for loss of visual field, the current standard of carefor adult-onset glaucoma includes treatment with IOP-lowering medications, which are typically delivered topicallyas eye drops. Unfortunately, the need for self-administration negatively affects patient compliance. Moreover,there are a limited number of drug families that are in use. In a major step toward addressing the limitations ofcurrently marketed IOP-lowering drops, we engineered a novel non-irritative microemulsion (ME) formulation thatprovides extended release of pregabalin (PRG)¾a repurposed FDA-approved drug with a new mechanism ofaction for IOP-lowering. While our ME has many features that position it to fill major gap in IOP management, itrequires daily self-dosing. To directly address this unmet clinical need, we will optimize and evaluate theIOP-lowering properties and safety of a subconjunctival biodegradable electrospun depot containingPRG. OculoTherapy's long-term research goal is to develop therapies that preserve vision in glaucoma patients.In this current SBIR Phase I application, we test the hypothesis that a subconjunctival depot comprised of slowlybiodegradable and biocompatible nanospun polymers can be engineered to provide zero order release ofPRG, which will maintain IOP in the physiological range until the depot is spent. Our objective is to ultimatelyachieve 4 months of release from a single subconjunctival injection. Our hypothesis is supportedour preliminary data demonstrating that PRG-loaded nanofibers comprised of a polymeric blend provide releaseof PRG with only 13% of loaded drug being released after 4 weeks, demonstrating that 4 months of release froma single depot is well within range. Overall strengths of this project include: 1) a strong and experiencedinterdisciplinary OculoTherapy team; 2) engineering of an innovative delivery strategy using a polymericbiocompatible depot that is expected to provide extended drug release; 3) the use of a highly promising FDA-approved drug that is being repurposed as a glaucoma therapeutic; and 4) the potential for a highly significantincrease in patient adherence because the need for daily input from the patient is eliminated. In this Phase I SBIRproposal, we provide proof-of-concept data and address key feasibility questions by establishing the safety andefficacy of a bioengineered subconjunctivally placed polymer depot. Aim 1: We test the hypothesis that asubconjunctival electrospun depot comprised of biodegradable and biocompatible polymers can provide up to 4months of zero order release of PRG. Several polymers and polymer blends will be evaluated either alone or incombination. Aim 2: We test the hypothesis that our subconjunctival PRG depot is biocompatible and efficacious.IOP and safety will be evaluated. Ocular biodistribution studies will also be performed. Minimum performancemetrics include: 1) a sustained decrease in IOP for ~4 months from a single depot; 2) no significant developmentof tolerance; and 3) an intraocular distribution of the drug that correlates with its effect on IOP reduction.
Public Health Relevance Statement: Because elevated intraocular pressure (IOP) and IOP fluctuations are the primary risk factors for loss of visual
field in glaucoma, the current standard of care for adult-onset glaucoma includes treatment with IOP-lowering
medications, which are typically delivered topically as eye drops because of their ease of use and the ability
for a patient to receive treatment from the comfort of their home. The requirement for multiple daily dosings
along with associated eye irritation in addition to orbital and systemic side effects noted in available
medications, collectively contribute to the low patient adherence documented by many eye care
specialists. To directly address this unmet clinical need to increase patient adherence, within these SBIR
Phase 1 studies, we will optimize and evaluate the IOP-lowering properties and safety of a subconjunctival
biodegradable electrospun depot containing PRG.
Project Terms: <21+ years old>
