Airborne Nanoparticles for Therapeutic Applications

描述(由申请人提供)：增殖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。许多药物已经被证明在抑制PVR方面是有效的；然而，还没有任何令人满意的方法将它们以安全的方式输送到视网膜。我们在该项目第一阶段的研究表明，空气中的纳米颗粒在将抗增殖药物输送到视网膜方面非常有希望；特别是在玻璃体切除后立即，当眼睛充满气体的时候。电喷雾和高频超声雾化可以在50-500 nm范围内产生所需的颗粒。这些空气悬浮颗粒被输送到猪模型的眼睛，并产生了令人满意的沉积动力学。基于上述微粒产生技术，建议建立一个自动化交钥匙药物纳米微粒发生器，该发生器将准备在眼科手术室使用。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给药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进行测试。这种联合药物将被输送到兔的PVR模型中，治疗后将进行为期10周的监测。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疗效。治疗的安全性将建立在视网膜成像、视网膜电图和组织病理学的基础上。除了5-FU的安全性和有效性研究外，高效药物丝裂霉素C(加或不加肝素)的有效性也将使用上述PVR模型进行检测。预计拟议的治疗方法将在第二阶段项目结束时准备好进行临床试验。该项目涉及增生性玻璃体视网膜病变(PVR)的治疗，即导致视网膜脱离的疤痕组织的生长，从而导致视网膜再附着手术的失败。将提供一种药物纳米颗粒生成器，使抗增殖剂能够有效地输送到视网膜。有效性和安全性研究将使用PVR的兔模型进行。我们预计在这个项目结束前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.