Airborne Nanoparticles for Therapeutic Applications

描述（由申请人提供）：摘要增生性玻璃体视网膜病变（PVR）或瘢痕组织生长是视网膜复位手术失败的主要原因。许多药物已被证明有效抑制PVR;然而，还没有任何令人满意的方法以安全的方式将它们递送到视网膜。我们在该项目第一阶段的研究表明，空气中的纳米颗粒非常有希望将抗增殖药物输送到视网膜;特别是在玻璃体切除术后，当眼睛充满气体时。电喷雾和高频超声雾化显示出产生50 - 500 nm范围内的所需颗粒。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。基于上述粒子生成技术，建议建立一个自动化交钥匙药物纳米粒子发生器，这将是准备用于眼科手术室。拟议的第二阶段项目还包括广泛的动物研究，以确定某些药物以气雾剂形式输送时的安全性和有效性。抗增殖药物5-FU将与低分子量肝素联合试验。将该组合药物递送至兔PVR模型，在治疗后监测10周。明尼苏达大学开发的PVR分级量表将用于记录上述治疗在不同剂量水平下的有效性。将根据视网膜成像、视网膜电图和组织病理学确定治疗的安全性。除了5-FU的安全性和疗效研究外，还将使用上述PVR模型检查高效药物丝裂霉素C（含或不含肝素）的疗效。预计到第二阶段项目结束时，拟议的治疗方法将准备好进行临床试验。该项目涉及增殖性玻璃体视网膜病变（PVR）的治疗，或导致视网膜脱离的瘢痕组织生长，因此，视网膜复位手术失败。将提供一种药物纳米颗粒发生器，其将使得能够将抗增殖剂有效递送至视网膜。将使用兔PVR模型进行疗效和安全性研究。我们希望在该项目结束时准备好进行临床试验。

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.