SBIR Phase I: Sustained Pulmonary Release of Nanoencapuslated Proteins for Counter Bioterrorism Applications

这个小企业创新研究（SBIR）项目的重点是一种新型的基于蛋白质的抗毒素的持续肺释放方法，用于对抗生物恐怖主义。目前迫切需要对诸如炭疽、霍乱、破伤风、白喉、蓖麻毒素等生物恐怖制剂进行治疗。这些生物毒素制剂的致死量非常小，从0.001微克/千克到0.1微克/千克不等。通常抗生素只对中和生物恐怖制剂（如细菌）有效，而对释放的蛋白质毒素无效。目前，在开发能够中和蛋白质生物毒素在人类环境中释放期间和之后的治疗方法方面存在重大挑战。这个探索性项目的总体目标是开发和证明完全纳米封装的亲水性蛋白质（如抗体、酶或基于蛋白质的细胞受体）的有效性，这些蛋白质可以通过肺部途径输送。这种粒子将使用一种新的半导体薄膜沉积技术合成，这种技术直到最近才被用于制药应用。肺部持续释放蛋白质不仅可以中和生物毒素，还可以传递其他药物。无溶剂药物包封系统的发展不仅有潜力用于肺部应用，也有潜力用于多肽、传统非多肽和基因治疗药物的注射和口服递送。许多疾病，如糖尿病、囊性纤维化和遗传性蛋白质缺乏症，都需要蛋白质和肽的有效递送。因此，这个项目可能会导致一种平台技术的发展，为多种疾病提供大分子。

This Small Business Innovation Research (SBIR) project focuses of novel method for sustained pulmonary release of protein based antitoxins for counter bioterrorism applications. There is a significant need of therapeutic treatments against bioterrorism agents such as anthrax, cholera, tetanus, diphtheria, ricin, etc. These biotoxin agents are lethal in very small amount ranging from 0.001 microg / kg to 0.1 microg / kg. Typically antibiotics are only effective in neutralizing the bioterrorism agent (e.g. bacterium) and not the released protein toxin. Significant challenges currently exist in the development of therapeutic methods that can neutralize the protein biotoxin during and after it has been released in the human environment . The overall goal of this exploratory project is to develop and demonstrate the effectiveness of completely nano-encapsulated hydrophilic proteins (such as antibodies, enzymes or protein based cell receptor) that can be delivered via the pulmonary route. Such particles will be synthesized using a novel semiconductor film deposition technique, which has until recently not been explored for pharmaceutical applications.Sustained Pulmonary release of proteins can not only neutralize biotoxin agents but also deliver other drugs. The development of solvent-free drug encapsulation systems has the potential to be used not only in pulmonary-based applications but also in injectable and oral delivery of peptide, traditional non-peptide and gene-therapy based drugs. Efficient delivery of proteins and peptides is required for a number of diseases such as diabetes, cystic fibrosis, and genetic protein deficiency disorders. Thus this project could lead to development of a platform technology for delivery of macromolecules for several diseases.