1. Synthesis, degradation, and antimicrobial properties of targeted macromolecular prodrugs of norfloxacin.
- Author
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Roseeuw E, Coessens V, Balazuc AM, Lagranderie M, Chavarot P, Pessina A, Neri MG, Schacht E, Marchal G, and Domurado D
- Subjects
- Animals, Anti-Infective Agents metabolism, Antitubercular Agents pharmacology, Bacteria drug effects, Bacterial Infections drug therapy, Bacterial Infections microbiology, Dextrans, Drug Carriers, Isoniazid pharmacology, Lung microbiology, Mannose, Mice, Mice, Inbred C57BL, Mycobacterium Infections drug therapy, Mycobacterium Infections microbiology, Mycobacterium bovis drug effects, Norfloxacin metabolism, Peptides chemical synthesis, Peptides metabolism, Peptides pharmacology, Prodrugs metabolism, Anti-Infective Agents chemical synthesis, Anti-Infective Agents pharmacology, Norfloxacin chemical synthesis, Norfloxacin pharmacology, Prodrugs chemical synthesis, Prodrugs pharmacology
- Abstract
Long-term antibiotic treatment is required to cure tuberculosis. Targeted antibiotics should improve the efficacy of treatment by concentrating the drugs close to the bacteria. The aim of the present study was to synthesize targeted conjugates. For this purpose, we used mannose as a homing device to direct norfloxacin into macrophages. Dextran was used as the polymer bearing both mannose and norfloxacin. Using different peptide spacer arms to link norfloxacin to dextran, we demonstrated that norfloxacin acts as an antibiotic only when it is released in its native form. Also, targeting by using mannose as a homing device is required to achieve antimycobacterial activity in vivo. Thus, norfloxacin, which is inactive against mycobacteria in its native form in vivo, can be transformed into an active drug by targeting.
- Published
- 2003
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