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Abstract
Grant Number: 1R43AI052986-01A1 PI Name: SCOTTO, ANTHONY W. PI Email: tscotto@transaveinc.com PI Title: Project Title: Therapeutic Targeting of the Infectious Path of Anthrax Abstract: 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.
Thesaurus Terms:
alveolar macrophage, anthrax, antibacterial agent, bacteria infection mechanism, biotherapeutic agent, lipid
drug design /synthesis /production, lymphatic system, macrophage, phagocytosis, respiratory epithelium
biotechnology, guinea pig
Institution: TRANSAVE, INC. 7 DEER PK DR, STE N MONMOUTH JUNCTION, NJ 08852 Fiscal Year: 2003 Department: Project Start: 01-JUL-2003 Project End: 31-DEC-2004 ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES IRG: ZRG1