Therapeutic Targeting of the Infectious Path of Anthrax

描述（由申请人提供）：炭疽常被误读为巨噬细胞/网状内皮系统（RES）的细胞内疾病。然而，它被更好地描述为一种招募巨噬细胞的疾病，首先是肺泡巨噬细胞进行其萌发，然后是系统性巨噬细胞（RES）完成其生化发病机制。只有在它从一个活化的孢子转变为新生的营养细胞的过程中，它才成为细胞内的乘客。这一过程发生在其从肺上皮通过肺泡巨噬细胞转移到肺淋巴的过程中或之前的某个时间点，这一萌发过程可能延长到近60天。正是在这个阶段，巨噬细胞对抗菌剂最敏感。一旦成熟的营养细胞发育，通常在肺淋巴感染病灶的2-6小时内，需要局部储存具有持续释放的抗生素以达到杀菌作用。我们认为，高靶向剂量的吸入slit -环丙沙星可以最好地预防并可能治愈病情，这也将减少长期治疗期间的全身剂量。最后，在炭疽广泛吸入暴露之后，我们期望高度靶向的slit -环丙沙星将满足对大量潜在受感染个体的快速，易于分发和高度可见的预防需求。

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.