Therapeutic Targeting of the Infectious Path of Anthrax

炭疽感染途径的治疗靶向

• 批准号: 6634356
• 负责人: ANTHONY W SCOTTO
• 金额: $ 10万
• 依托单位: TRANSAVE, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6634356
• 关键词: alveolar macrophages; anthrax; antibacterial agents; bacteria infection mechanism; biotechnology; biotherapeutic agent; drug design /synthesis /production; guinea pigs; lipids; lymphatic system; macrophage; phagocytosis; respiratory epithelium

DESCRIPTION (provided by applicant): Anthrax is often misrepresented as an intracellular disease of the macrophages/reticuloendothelial system (RES). It is, however, better characterized as a disease that recruits macrophages, first alveolar macrophages for its germination and then systemic macrophages (RES) to complete its biochemical pathogenesis. Only during its transformation from an activated spore to a nascent vegetative cell is it an intracellular passenger. This process occurs at some point during or prior to its translocation from the pulmonary epithelium, via the alveolar macrophages to the pulmonary lymphatics, the time course of this germination may extend to almost 60 days. It is at this stage in the macrophage that it is most susceptible to antimicrobial agents. Once a mature vegetative cell develops, usually within 2-6 hours at the foci of the infection in the pulmonary lymphatics, a localized depot of antibiotic with a sustained release needs to be present to be bactericidal. We believe a prophylactic and possibly a curative condition can be best achieved by a highly targeted dose of inhalation SLIT-ciprofloxacin, which will also reduce systemic dosage during prolonged therapy. Lastly, in the aftermath of a widespread inhalation exposure to anthrax we expect that a highly targeted SLIT-ciprofloxacin will address the need for a rapid, easily dispensed and highly visible prophylaxis for large numbers of potentially afflicted individuals.

描述（由申请人提供）：炭疽经常被误认为是巨噬细胞/网状内皮系统（RES）的细胞内疾病。然而，它更好地被描述为一种招募巨噬细胞的疾病，首先是肺泡巨噬细胞用于其萌发，然后是系统性巨噬细胞（RES）以完成其生化发病机制。只有在从活化的孢子转变为新生营养细胞的过程中，它才是细胞内的乘客。这个过程发生在肺上皮从肺上皮通过肺泡巨噬细胞转移到肺淋巴管期间或之前的某个时刻，这个发芽的时间过程可能会延长到近 60 天。巨噬细胞在这个阶段最容易受到抗菌剂的影响。一旦成熟的营养细胞发育，通​​常在肺淋巴管感染灶处 2-6 小时内，就需要存在持续释放的局部抗生素库以起到杀菌作用。我们相信，通过高度针对性的吸入SLIT-环丙沙星剂量可以最好地实现预防性和可能的​​治疗性，这也将减少长期治疗期间的全身剂量。最后，在广泛吸入炭疽后，我们预计高度针对性的 SLIT-环丙沙星将满足对大量潜在患病个体进行快速、易于分配和高度可见的预防的需求。