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.

项目摘要 1600万美国人被诊断出患有干眼病，可能会遭受此问题的痛苦。 女性的患病率更高，随着年龄的增长而增加，现在在18-34岁的人中也值得注意 年。它的特征是失去泪膜的体内平衡，可能伴随着持续的 如果未经治疗，会对角膜和结膜造成炎症损害的刺激或燃烧症状。 当前通过减少眼部炎症而起作用的目前眼睛吸收治疗有几个 可能会让患者感到沮丧的缺陷。免疫调节剂Cyclosporine通常在 这些用各种送货车在包括阴离子乳液，阳离子纳米乳胶或 纳米细胞溶液。但是，车辆对延长角膜居住地的影响仍然受到限制 天然的眼防机制。人们认为这是普通干眼症的原因之一 在临床试验中，通过这种眼部滴剂的治疗没有更好或更快的效率。项目团队提出的建议 将环孢菌素掺入隐形眼镜中，以更好地输送活性成分，并有可能更少的侧面 剂量可以更好地控制剂量。众所周知，从隐形眼镜输送药物会导致几个 由于将药物直接转移到角膜上的薄撕裂层上，因此比眼滴高的生物利用度高。 使用我们的双层隐形眼镜平台和充电边界层技术，我们将解决缺陷 通过（1）使用药物以（1）在低浓度下持续8小时的环孢菌素的治疗 洗脱隐形眼镜，以便精确积累环孢霉素在角膜表面上，（2）输送 环孢素从新型药物洗脱隐形眼镜中加载阳离子纳米载体，以改善纳米载体 对角膜和结膜表面的粘附，并增强环孢菌素渗透到前腔中， （3）进行纳米载体的体外细胞基于基于细胞的细胞毒性研究，并通过体内猪 眼睛模型测量环孢菌素角膜渗透效率洗脱了隐形眼镜。