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.

项目概要 一千六百万美国人被诊断患有干眼症，可能还有更多的人患有此问题。 女性的患病率较高，且随着年龄的增长而增加，目前在 18-34 岁的人群中也很显着 其特点是泪膜稳态丧失，并可能伴有持续的症状。 如果不及时治疗，可能会导致角膜和结膜发炎性损伤的刺激或烧灼症状。 目前通过减少眼科炎症起作用的滴眼剂有几种 免疫调节剂环孢菌素的缺陷可能会让患者感到沮丧。 这些滴眼剂使用多种递送载体，包括阴离子乳液、阳离子纳米乳液或 然而，纳米胶束解决方案对延长角膜停留时间的影响仍然有限。 这被认为是常见干眼病的原因之一。 项目组建议，此类眼药水的治疗在临床试验中并没有更好或更快的疗效。 将环孢菌素加入隐形眼镜中，以更好地输送活性成分，并可能减少副作用 众所周知，隐形眼镜的药物输送可导致多种效果。 由于药物通过薄泪层直接转移到角膜，因此生物利用度比滴眼剂高一倍。 使用我们的双层隐形眼镜平台和带电边界层技术，我们将解决这些缺陷 目前的治疗方法如下：(1) 使用药物持续递送低浓度环孢素 8 小时/天 洗脱隐形眼镜，使环孢菌素在角膜表面精确积聚，(2) 新型药物洗脱隐形眼镜中负载环孢菌素的阳离子纳米载体，以改进纳米载体 粘附角膜和结膜表面并增强环孢菌素渗透到前房中， (3) 通过离体猪进行纳米载体的体外细胞毒性研究 眼模型测量环孢素角膜渗透药物洗脱隐形眼镜装置的功效。