Airborne Nanoparticles for Therapeutic Applications

增生性玻璃体视网膜病变（PVR），或瘢痕组织的生长，是视网膜再附着手术失败的主要原因。许多药物已被证明对抑制PVR有效；然而，目前还没有任何令人满意的方法可以安全地将它们运送到视网膜。我们在这个项目的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，眼睛充满气体的时候。电喷涂和高频超声雾化均能在50 ~ 500nm范围内产生理想的颗粒。这些空气中的颗粒被输送到猪模型的眼睛中，并产生了令人满意的沉积动力学。在上述粒子生成技术的基础上，提出构建自动化交钥匙式药物纳米粒子发生器，可用于眼科手术室。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溶胶形式输送时的安全性和有效性。抗增殖药物5-FU将与低分子肝素联合试验。该联合药物将给予兔PVR模型，治疗后监测10周。将使用明尼苏达大学开发的PVR分级量表来记录不同剂量水平下上述治疗的有效性。治疗的安全性将根据视网膜成像、视网膜电图和组织病理学来确定。除了5-FU的安全性和有效性研究外，还将使用上述PVR模型检查强效药物丝裂霉素C（加或不加肝素）的疗效。预计该疗法将在二期项目结束时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，或疤痕组织的生长导致视网膜脱离，因此，视网膜再附着手术失败。将提供一种药物纳米颗粒发生器，使抗增殖剂能够有效地输送到视网膜。将使用兔PVR模型进行疗效和安全性研究。我们期望在这个项目结束时为临床试验做好准备。

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.