Propst Crystal N, Nwabueze Albert O, Kanev Igor L, Pepin Rachel E, Gutting Bradford W, Morozov Victor N, van Hoek Monique L
School of Systems Biology and National Center for Biodefense and Infectious Diseases, George Mason University, MS1H8, Manassas, VA, 20110, USA.
Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
J Nanobiotechnology. 2016 Apr 18;14:29. doi: 10.1186/s12951-016-0182-0.
The Institute of Theoretical and Experimental Biophysics in Moscow recently developed a new nanoaerosol generator. This study evaluated this novel technology, which has the potential to enhance therapeutic delivery, with the goal of using the generator to treat pulmonary Francisella tularensis subsp. novicida (F. novicida) infections in BALB/c mice.
First, the analysis of quantum dots distribution in cryosections of murine lungs demonstrated that nanoaerosols penetrate the alveoli and spread more homogenously in the lungs than upon intranasal delivery. Second, the generator was used to aerosolize the antibiotic levofloxacin to determine the effectiveness of nanoaerosolized levofloxacin as treatment against F. novicida. The generator was capable of delivering a sufficient dose of nanoaerosolized liposome-encapsulated levofloxacin to rescue mice against 100LD50 of F. novicida.
The nanoaerosol-delivered dosage of liposome-encapsulated levofloxacin required to rescue mice is approximately 94× lower than the oral required dose and approximately 8× lower than the intraperitoneal dose required for rescue. In addition, treatment with nanoaerosols consumes less total volume of therapeutic solutions and is gentler on sprayed material than the aerosolization by a conventional three-jet Collison nebulizer as seen by the preservation of liposomes. This could represent a significant advance for the use of expensive therapeutics and lung directed therapies.
莫斯科理论与实验生物物理研究所最近研发出一种新型纳米气溶胶发生器。本研究对这项具有增强治疗给药潜力的新技术进行了评估，目的是使用该发生器治疗BALB/c小鼠肺部的土拉热弗朗西斯菌新凶手亚种（F. novicida）感染。
首先，对小鼠肺冰冻切片中量子点分布的分析表明，纳米气溶胶能够穿透肺泡，并且在肺内的扩散比经鼻给药时更均匀。其次，使用该发生器将抗生素左氧氟沙星雾化，以确定纳米雾化左氧氟沙星治疗F. novicida的有效性。该发生器能够输送足够剂量的纳米雾化脂质体包裹左氧氟沙星，使小鼠抵御100LD50的F. novicida。
拯救小鼠所需的纳米气溶胶递送的脂质体包裹左氧氟沙星剂量比口服所需剂量低约94倍，比腹腔注射所需的拯救剂量低约8倍。此外，与传统三射流碰撞雾化器雾化相比，纳米气溶胶治疗消耗的治疗溶液总体积更少，对喷雾材料的损伤更小，如脂质体的保存情况所示。这对于昂贵治疗药物的使用和肺部定向治疗而言可能是一项重大进展。
