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

这一小型企业创新研究(SBIR)项目关注的是用于抗生物恐怖主义应用的蛋白质类抗毒素在肺部持续释放的新方法。对炭疽、霍乱、破伤风、白喉、蓖麻毒素等生物恐怖分子的治疗非常有必要。这些生物毒素在0.001微克/公斤至0.1微克/公斤的极少量范围内是致命的。通常，抗生素只对中和生物恐怖分子(如细菌)有效，而不是对释放的蛋白质毒素有效。目前在开发治疗方法方面存在重大挑战，这些方法可以在蛋白质生物毒素在人类环境中释放期间和之后中和它。这一探索性项目的总体目标是开发和展示完全纳米包裹的亲水性蛋白质(如抗体、酶或基于蛋白质的细胞受体)的有效性，这种蛋白质可以通过肺部途径输送。这种微粒将使用一种新的半导体薄膜沉积技术来合成，这种技术直到最近才被探索用于药物应用。蛋白质的持续肺释放不仅可以中和生物毒素，还可以输送其他药物。无溶剂型药物包囊系统的开发不仅可用于肺部药物，还可用于多肽、传统非多肽和基因治疗药物的注射和口服给药。许多疾病，如糖尿病、囊性纤维化和遗传性蛋白缺乏症，都需要有效的蛋白质和多肽输送。因此，该项目可能导致开发一种平台技术，用于为几种疾病提供大分子。

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.