SBIR-STTR Award

Sixteen million Americans are diagnosed with dry eye disease, with likely many more suffering from this issue.Prevalence is higher among women, increases with age, and is now also notable among those aged 18-34years. It is characterized by a loss of homeostasis of the tear film and may be accompanied by persistentsymptoms of irritation or burning that can cause inflammatory damage to the cornea and conjunctiva if untreated.Current eye-drop treatments that work by reducing the inflammation on the ocular service have severaldeficiencies that can be frustrating for patients. The immunomodulator, cyclosporine, is commonly prescribed inthese eye drops using a variety of delivery vehicles including anionic emulsions, cationic nanoemulsions, ornanomicellar solutions. However, the impact of the vehicle to prolong corneal residence is still limited due tonatural ocular defensive mechanisms. This is believed to be one reason that the common dry eye diseasetreatment by such eye drops do not have better or faster efficacy in clinical trials. The project team proposes toincorporate cyclosporine into a contact lens to better deliver the active ingredient and potentially with fewer sideeffects as the dosing is better controlled. It is known that drug delivery from a contact lens can result in severaltimes higher bioavailability than eye drops due to the direct transfer of a drug to cornea across a thin tear layer.Using our dual layer contact lens platform and charged boundary layer technology we will resolve the deficienciesof current therapy by (1) Delivering cyclosporine at low concentration consistently for 8 hours/day using a drugeluting contact lens to allow a precise accumulation of cyclosporine on corneal surface, (2) Deliveringcyclosporine loaded cationic nanocarriers from a novel drug eluting contact lens to improve the nanocarrieradhesion to cornea and conjunctiva surface and enhance cyclosporine penetration into the anterior chamber,(3) Conducting in vitro cell-based cytotoxicity studies of the nanocarriers and by means of an ex vivo porcineeye model measure cyclosporine corneal penetration efficacy of the drug eluting contact lens devices.

Public Health Relevance Statement:
PROJECT NARRATIVE In the United States, over 16 million individuals are diagnosed with dry eye disease and often with suboptimal outcomes because of poor adherence and limited effectiveness of prescribed topical eye drop medications. Dry eye disease can substantially affect vision and quality of life, as symptoms often interfere with daily activities, and prevalence rates range from 5% to 50%, but can be as high as 75% among adults over age 40, with women most often affected. We propose to develop a novel contact lens device for treatment of dry eye disease that can precisely transport anti-inflammation agents to the eye with the therapeutic agent(s) delivered even more effectively by incorporation of ocular penetrating nanocarriers.

Project Terms:
Adhesions ; Adsorption ; Adult ; 21+ years old ; Adult Human ; adulthood ; Affect ; Age ; ages ; Animals ; anterior chamber ; Autoimmune Responses ; Biological Availability ; Bioavailability ; Biologic Availability ; Physiologic Availability ; Cations ; Cell physiology ; Cell Function ; Cell Process ; Cellular Function ; Cellular Physiology ; Cellular Process ; Subcellular Process ; Cells ; Cell Body ; Centers for Disease Control and Prevention (U.S.) ; CDC ; Centers for Disease Control ; Centers for Disease Control and Prevention ; United States Centers for Disease Control ; United States Centers for Disease Control and Prevention ; Charge ; Clinical Trials ; conjunctiva ; Contact Lenses ; Hydrophilic Contact Lenses ; Soft Contact Lenses ; Cornea ; corneal ; Keratoplasty ; Cornea Transplantation ; Corneal Grafting ; Corneal Transplantation ; corneal keratoplasty ; corneal transplant ; Cyclosporine ; Ciclosporin ; CsA ; Cyclosporin A ; Cyclosporine A ; Sandimmun ; SangCya ; neoral ; sandimmune ; Diagnosis ; Diffusion ; Disease ; Disorder ; Dosage Forms ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Dry Eye Syndromes ; Dry eye disease ; Keratoconjunctivitis Sicca ; Emulsions ; Engineering ; Environment ; Eye ; Eyeball ; Eyedrops ; Eye Drops ; Graft Rejection ; Transplant Rejection ; Transplantation Rejection ; Homeostasis ; Autoregulation ; Physiological Homeostasis ; Human ; Modern Man ; Immunosuppressive Agents ; Immunosuppressants ; Immunosuppressive drug ; Immunosuppressive treatment ; immune suppressive agent ; immune suppressor ; immunosuppressive substance ; immunosuppressor ; In Vitro ; Inflammation ; Institutes ; Penetrating Keratoplasty ; Kinetics ; Oleic Acids ; 9-Octadecenoic Acid ; cis-9-Octadecenoic Acid ; Oxygen ; O element ; O2 element ; Patients ; Permeability ; Play ; Polyethylene Glycols ; Macrogols ; Polyethylene Oxide ; Polyethyleneoxide ; Polyoxyethylenes ; Quality of life ; QOL ; Role ; social role ; Silicones ; Solubility ; Sphingolipids ; Family suidae ; Pigs ; Suidae ; Swine ; porcine ; suid ; T-Lymphocyte ; T-Cells ; thymus derived lymphocyte ; Technology ; Thinness ; Leanness ; Time ; Tissues ; Body Tissues ; Translating ; United States ; Vision ; Sight ; visual function ; Woman ; Work ; Generations ; Measures ; Drug Delivery Systems ; Drug Delivery ; Film ; base ; dosage ; improved ; Procedures ; Prophylactic treatment ; Prophylaxis ; Surface ; Penetration ; Phase ; Physiological ; Physiologic ; residence ; residential building ; residential site ; Individual ; Hypoxia ; Hypoxic ; Oxygen Deficiency ; uptake ; Functional disorder ; Dysfunction ; Physiopathology ; pathophysiology ; Immunological response ; host response ; immune system response ; immunoresponse ; Immune response ; Therapeutic ; Therapeutic Agents ; Inflammatory ; Electrostatics ; Hour ; Severities ; irritation ; corneal epithelial ; corneal epithelium ; Services ; American ; biocompatibility ; biomaterial compatibility ; Lytotoxicity ; cytotoxicity ; success ; drug efficacy ; lipophilicity ; aqueous ; Hydrogels ; Toxicities ; Toxic effect ; novel ; Devices ; Modeling ; nano tech ; nano technology ; nano-technological ; nanotech ; nanotechnological ; Nanotechnology ; α-Tocopherol ; alpha Tocopherol ; Conjunctival Epithelium ; Effectiveness ; Causality ; causation ; disease causation ; Etiology ; cell mediated immune response ; Dose ; Symptoms ; Adherence ; Dryness ; Organ Model ; Immunomodulators ; IMiD ; Immune modulatory therapeutic ; immune modulating agents ; immune modulating drug ; immune modulating therapeutics ; immune modulators ; immune modulatory agents ; immune modulatory drugs ; immunomodulating agents ; immunomodulatory agents ; immunomodulatory drugs ; immunomodulatory therapeutics ; nanocarrier ; nano carrier ; nanoemulsion ; nano emulsion ; Treatment Efficacy ; intervention efficacy ; therapeutic efficacy ; therapy efficacy ; Outcome ; Population ; ocular surface ; Prevalence ; aged ; surfactant ; novel therapeutics ; new drug treatments ; new drugs ; new therapeutics ; new therapy ; next generation therapeutics ; novel drug treatments ; novel drugs ; novel therapy ; prototype ; lens ; lenses ; effective therapy ; effective treatment ; Biological Markers ; bio-markers ; biologic marker ; biomarker ; arm ; Formulation ; persistent symptom ; chronic symptom ; side effect ;

Sixteen million Americans are diagnosed with dry eye disease, with likely many more suffering from this issue.Prevalence is higher among women, increases with age, and is now also notable among those aged 18-34years. It is characterized by a loss of homeostasis of the tear film and may be accompanied by persistentsymptoms of irritation or burning that can cause inflammatory damage to the cornea and conjunctiva if untreated.Current eye-drop treatments that work by reducing the inflammation on the ocular service have severaldeficiencies that can be frustrating for patients. The immunomodulator, cyclosporine, is commonly prescribed inthese eye drops using a variety of delivery vehicles including anionic emulsions, cationic nanoemulsions, ornanomicellar solutions. However, the impact of the vehicle to prolong corneal residence is still limited due tonatural ocular defensive mechanisms. This is believed to be one reason that the common dry eye diseasetreatment by such eye drops do not have better or faster efficacy in clinical trials. In this Phase II project, wepropose continuing the successful development of a drug delivery contact lens (DDCL) designed to manage dryeye by incorporating cyclosporine A (CsA) to better deliver the active ingredient with fewer side effects due tobetter control of dosing. An important discovery in Phase I was the use of hyaluronic acid (HA) improving CsAuptake and retention, with the potential for faster relief of symptoms due to HA's own lubricating and regenerativeproperties as a naturally occurring substance in the body. With the key aims of Phase I substantially completed,Phase II will focus on optimizing the DDCL with CsA and HA using active ingredients sourced from commercialmanufacturers, and lenses with FDA 510(k) clearance for which we have rights to commercial use. The productcan then be easily integrated into an existing contact lens production process for use in clinical trials followingthe project. Successful completion of the Phase II research strategy will include positive results by in vivo studyand an IND application for clinical study of the DDCL in a human population. For the commercialization strategy,we have agreement with a global contact lens company to manufacture and supply the DDCL, and arenegotiating a licensing agreement with this partner for selected regions. Investment and future royalties from thepartner will allow our independent development of the DDCL for other markets in the future.

Public Health Relevance Statement:
PROJECT NARRATIVE Dry eye disease is one of the most common worldwide ophthalmic conditions, affecting at least sixteen million Americans, in addition to millions more undiagnosed cases that will all rise substantially due to the continuing growth of inflammatory disorders and screen time among the population. In this SBIR Phase II project, we propose to continue the successful development of a drug delivery contact lens (DDCL) that administers cyclosporine A (CsA) using a novel formulation of nano-ingredients to resolve key deficiencies of eye drop formulations; for example, limited bioavailability, both from tear wash-out and vehicular compromises required to solubilize the drug ingredient. The Phase II research strategy will culminate in an IND application for clinical study of the DDCL in a human population, while the commercialization strategy's goal is the development of the product for FDA approval in the US, with the support of a licensing agreement and investment from an established industrial partner.

Project Terms:
<21+ years old>