Airborne Nanoparticles for Therapeutic Applications

用于治疗应用的气载纳米颗粒

• 批准号: 7503342
• 负责人: AMIR A NAQWI
• 金额: $ 38.07万
• 依托单位: POWERSCOPE, INC
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7503342
• 关键词: Aerosols; Aftercare; Air; Animals; Arts; Biological Assay; Breathing; Budgets; Caliber; Chemopreventive Agent; Cicatrix; Clinic; Clinical Trials; Conduct Clinical Trials; DL-alpha-Difluoromethylornithine; Data; Deposition; Depth; Development; Devices; Dose; Drug Combinations; Drug usage; Effectiveness; Electroretinography; Equipment; Evaluation; Eye; Eye Part; Failure; Family suidae; Fluorouracil; Frequencies; Future; Gases; Generations; Goals; Growth; Heparin; High Pressure Liquid Chromatography; Histopathology; Hospitals; Hour; Image; Infusion procedures; Just-in-time-concept; Kinetics; Left; Low-Molecular-Weight Heparin; Lung; Malignant neoplasm of lung; Metabolic Clearance Rate; Methods; Minnesota; Mitomycin; Modeling; Molecular Weight; Monitor; Mus; Operating Rooms; Operative Surgical Procedures; Ophthalmologist; Ophthalmology; Oryctolagus cuniculus; Output; Particle Size; Pharmaceutical Preparations; Phase; Prevention; Procedures; Proliferative Vitreoretinopathy; Purpose; Range; Rate; Research; Retina; Retinal; Retinal Detachment; Safety; Sodium Fluorescein; Solutions; Standards of Weights and Measures; Sus scrofa; System; Technology; Testing; Therapeutic; Time; Tissues; Treatment Efficacy; Tube; Ultrasonics; United States Food and Drug Administration; Universities; Vendor; Vitrectomy; Week; Work; aerosolized; air cleaner; aqueous; base; cancer therapy; comparative; desire; dosage; drug development; lens; nanoparticle; new technology; particle; prototype; size; submicron; tool

DESCRIPTION (provided by applicant): Summary Proliferative Vitreoretinopathy (PVR), or growth of scar tissues, is a major cause for the failure of retinal re-attachment surgeries. Many drugs have been proven effective in suppressing PVR; however, there has not been any satisfactory means to deliver them to the retina in a safe manner. Our research in Phase I of this project has shown that airborne nanoparticles are very promising for the delivery of anti-proliferative drugs to the retina; in particular, immediately after vitrectomy, when the eye is filled with gas. Electrospraying and high-frequency ultrasonic nebulization are shown to generate desired particles in 50 - 500 nm range. These airborne particles were delivered to the eye of a pig model and resulted in satisfactory deposition kinetics. Based on the above particle-generation technologies, it is proposed to build an automated turnkey drug nanoparticle generator, which would be ready for use in ophthalmology operating rooms. Proposed Phase II project also covers extensive animal studies to determine the safety and efficacy of certain drugs, when delivered in the form of aerosols. The anti-proliferative drug 5-FU will be tested in combination with low molecular weight heparin. This combination drug will be delivered to PVR models of rabbits, which will be monitored for 10 weeks after the treatment. A PVR grading scale developed at the University of MN will be used to record the effectiveness of the above treatment for different dose levels. Safety of the treatment will be established on the basis of retinal imaging, electroretinography and histopathology. Besides the safety and efficacy study with 5-FU, efficacy of a highly potent drug, Mitomycin C (with or without heparin), will also be examined using the above PVR models. It is anticipated that the proposed treatment would be ready for clinical trials by the end of the Phase II project. This project deals with the treatment of proliferative vitreoretinopathy (PVR), or the growth of scar tissues that cause retinal detachment and hence, the failure of retinal re-attachment surgery. A drug nanoparticle generator would be provided that would enable effective delivery of anti-proliferative agents to the retina. Efficacy and safety studies will be undertaken using a rabbit model of PVR. We expect to be ready for clinical trials by the end of this project.

描述（由申请人提供）：摘要增生性玻璃体病（PVR）或疤痕组织的生长是视网膜重新连接手术失败的主要原因。事实证明，许多药物可有效抑制PVR；但是，没有任何令人满意的方式以安全的方式将其交付给视网膜。我们在该项目的第一阶段的研究表明，空中纳米颗粒对于向视网膜提供抗增殖药物非常有希望。尤其是在玻璃体切除术后，当眼睛充满气体时。电抛光和高频超声雾化显示可在50-500 nm范围内产生所需的颗粒。这些空气传播的颗粒被输送到猪模型的眼睛，并导致令人满意的沉积动力学。根据上述粒子生成技术，建议建立一个自动的交钥匙药物纳米颗粒发生器，该发电机可以准备在眼科手术室中使用。拟议的II期项目还涵盖了广泛的动物研究，以确定以气溶胶形式递送的某些药物的安全性和功效。抗增殖性药物5-FU将与低分子量肝素结合进行测试。该组合药物将被输送到兔子的PVR模型，该模型将在治疗后10周内进行监测。在明尼苏达大学开发的PVR分级量表将用于记录上述治疗方法对不同剂量水平的有效性。治疗的安全将根据视网膜成像，电视图和组织病理学建立。除了使用5-FU的安全性和功效研究外，还将使用上述PVR模型检查高度有效药物丝裂霉素C（有或没有肝素）的功效。预计在II期项目结束时，拟议的治疗将准备好进行临床试验。该项目涉及增生性玻璃体病（PVR）的治疗，或引起视网膜脱离的疤痕组织的生长，因此是视网膜重新辅助手术的失败。将提供一种药物纳米颗粒发生器，该发电机将有效地递送抗增殖剂向视网膜递送。将使用PVR的兔模型进行功效和安全研究。我们希望在该项目结束时准备好进行临床试验。