Synthesis, degradation, and antimicrobial properties of targeted macromolecular prodrugs of norfloxacin.
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.
Biomaterial and Polymer Research Group, Department of Organic Chemistry, University of Ghent, 9000 Ghent, Belgium.
Eveline
E
Roseeuw
Veerle
V
Coessens
Anne-Marie
AM
Balazuc
Micheline
M
Lagranderie
Pierre
P
Chavarot
Augusto
A
Pessina
Maria Grazia
MG
Neri
Etienne
E
Schacht
Gilles
G
Marchal
Dominique
D
Domurado
D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D003911:Dextrans; D004337:Drug Carriers; D007538:Isoniazid / Q000494:pharmacology; D008168:Lung / Q000382:microbiology; D008358:Mannose; D051379:Mice; D008810:Mice, Inbred C57BL; D009164:Mycobacterium Infections / Q000188:drug therapy / Q000382:microbiology; D009163:Mycobacterium bovis / Q000187:drug effects; D009643:Norfloxacin / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*
D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D003911:Dextrans; D004337:Drug Carriers; D010455:Peptides; D011355:Prodrugs; D009643:Norfloxacin; D008358:Mannose; D007538:Isoniazid