Respirable ciprofloxacin aerosol for inhaled anthrax

描述(申请人提供)：通过肺部输送固体环丙沙星气雾剂颗粒是一种诱人的可能性，可以将炭疽孢子追逐到胸腔淋巴结，并在孢子萌发时杀死细菌。 该项目的总体目标是开发一种方法，在这种方法中，吸入的微米级环丙沙星颗粒可用于使吸入性炭疽病患者受益。我们假设，雾化吸入的环丙沙星颗粒将被肺泡巨噬细胞摄取并运输到胸腔淋巴结，在那里吸入的炭疽孢子生长成活性细菌。我们的策略是在肺和淋巴部位的肺泡巨噬细胞内持续给予高浓度的抗生素。我们预计，随着环丙沙星颗粒的溶解，药物可能会在含有或接近含有孢子的其他细胞的肺泡巨噬细胞内释放，并能够在细菌萌发时杀死细菌。尽管包括妥布霉素在内的几种水溶性抗生素已经被配制成吸入气雾剂用于肺部给药，但环丙沙星等高亲脂抗生素的可呼吸颗粒还没有，尽管其他公司正在研究脂质体环丙沙星的形成。我们开发了一种基于超临界二氧化碳作为溶剂和推进剂的亲脂性药物气雾剂输送的有效方法。 我们这一试点项目的目标是确定超临界流体药物雾化吸入是否允许环丙沙星吸入到肺部，确定环丙沙星颗粒在培养的肺泡巨噬细胞中的摄取和溶解特性，研究环丙沙星颗粒在胸腔淋巴结的转运，并确定药代动力学参数。我们的总体目标是为炭疽孢子吸入受害者创造一种有针对性的治疗或预防的新工具。

DESCRIPTION (provided by applicant): Pulmonary delivery of solid ciprofloxacin aerosol particles is an attractive possibility for chasing anthrax spores into the thoracic lymph nodes and killing the bacteria when the spores germinate. The overall goal of this project is to develop a method in which inhaled micron-sized particles of ciprofloxacin can be used to benefit victims of inhalational anthrax. We hypothesize that aerosol administered particles of Upophilic ciprofloxacin will be taken up by alveolar macrophages and transported to the thoracic lymph nodes where inhaled anthrax spores vegetate into active bacteria. Our strategy is intended to put the antibiotic at high and sustained concentrations within alveolar macrophages in lung and lymph locations. We anticipate that as the ciprofloxacin particles dissolve, the drug may be released within alveolar macrophages that contain or are near to other cells that contain spores, and be able to kill the bacteria when they germinate. Although several water-soluble antibiotics, including tobramycin, have been formulated for pulmonary delivery as inhaled aerosols, respirable particles of highly lipophilic antibiotics like ciprofloxacin have not, although others are examining the formation of liposomal ciprofloxacin. We have developed an effective method for aerosol delivery of lipophilic drugs based on the use of supercritical carbon dioxide as solvent and propellant. Our goals for this pilot project are to determine whether supercritical fluid drug aerosolization will allow inhalation delivery of ciprofloxacin to the lungs, to determine the uptake and dissolution properties of ciprofloxacin particles in cultured alveolar macrophages, to investigate ciprofloxacin particle translocation to the thoracic lymph nodes, and to determine the pharmacokinetic parameters. Our overall goal is to create a new tool for targeted treatment or prophylaxis for victims of anthrax spore inhalation.