Sustained delivery technology for Cyclosporine A in the treatment of autoimmune response

环孢素 A 持续递送技术治疗自身免疫反应

• 批准号: 10256580
• 负责人: Roman Domszy
• 金额: $ 30万
• 依托单位: LYNTHERA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10256580
• 关键词: Adherence; Adhesions; Adsorption; Adult; Affect; Age; American; Animals; Autoimmune Responses; Biological Availability; Biological Markers; Cations; Cell physiology; Cells; Centers for Disease Control and Prevention (U.S.); Charge; Clinical Trials; Conjunctival Epithelium; Contact Lenses; Cornea; Cyclosporine; Devices; Diagnosis; Diffusion; Disease; Dosage Forms; Dose; Drug Delivery Systems; Dry Eye Syndromes; Dryness; Effectiveness; Electrostatics; Emulsions; Engineering; Environment; Etiology; Eye; Eyedrops; Family suidae; Film; Formulation; Functional disorder; Generations; Graft Rejection; Homeostasis; Hour; Human; Hydrogels; Hydrophilic Contact Lenses; Hypoxia; Immune response; Immunomodulators; Immunosuppressive Agents; In Vitro; Individual; Inflammation; Inflammatory; Institutes; Keratoplasty; Kinetics; Measures; Modeling; Nanotechnology; Oleic Acids; Organ Model; Outcome; Oxygen; Patients; Penetrating Keratoplasty; Penetration; Permeability; Pharmaceutical Preparations; Phase; Physiological; Play; Polyethylene Glycols; Population; Prevalence; Procedures; Prophylactic treatment; Quality of life; Role; Services; Severities; Silicones; Solubility; Sphingolipids; Surface; Symptoms; T-Lymphocyte; Technology; Therapeutic; Therapeutic Agents; Thinness; Time; Tissues; Toxic effect; Translating; Treatment Efficacy; United States; Vision; Woman; Work; aged; alpha Tocopherol; anterior chamber; aqueous; arm; base; biomaterial compatibility; cell mediated immune response; conjunctiva; corneal epithelium; cytotoxicity; dosage; drug efficacy; effective therapy; improved; irritation; lens; lipophilicity; nanocarrier; nanoemulsion; novel; novel therapeutics; ocular surface; persistent symptom; prototype; residence; side effect; success; surfactant; uptake

PROJECT SUMMARY 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 18–34 years. It is characterized by a loss of homeostasis of the tear film and may be accompanied by persistent symptoms 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 several deficiencies that can be frustrating for patients. The immunomodulator, cyclosporine, is commonly prescribed in these eye drops using a variety of delivery vehicles including anionic emulsions, cationic nanoemulsions, or nanomicellar solutions. However, the impact of the vehicle to prolong corneal residence is still limited due to natural ocular defensive mechanisms. This is believed to be one reason that the common dry eye disease treatment by such eye drops do not have better or faster efficacy in clinical trials. The project team proposes to incorporate cyclosporine into a contact lens to better deliver the active ingredient and potentially with fewer side effects as the dosing is better controlled. It is known that drug delivery from a contact lens can result in several times 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 deficiencies of current therapy by (1) Delivering cyclosporine at low concentration consistently for 8 hours/day using a drug eluting contact lens to allow a precise accumulation of cyclosporine on corneal surface, (2) Delivering cyclosporine loaded cationic nanocarriers from a novel drug eluting contact lens to improve the nanocarrier adhesion 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 porcine eye model measure cyclosporine corneal penetration efficacy of the drug eluting contact lens devices.

项目总结