Poly(ethylene glycol) transport forms of vancomycin: a long-lived continuous release delivery system.
The facile reaction of vancomycin with various PEG linkers, at the V(3) position, has been selectively accomplished by using an excess of base in DMF. Using rPEG as a blocking group for V(3) provides crystalline derivatives that can be further PEGylated to give pure V(3)-X(1) latentiated species (transport forms). V(3) tetrameric species were also prepared in order to increase the loading of drug on PEG. All PEG-vancomycin transport forms show significant antibacterial activity that is on the same order of native vancomycin. Significant increases in the AUC were observed for all PEG-vancomycin conjugates thus making them potential single dose therapies.
Enzon Pharmaceuticals Inc., 20 Kingsbridge Road, Piscataway, New Jersey 00854, USA. richard.greenwald@enzon.com
Richard B
RB
Greenwald
Hong
H
Zhao
Jing
J
Xia
Anthony
A
Martinez
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D001692:Biological Transport; D003460:Crystallization; D019281:Dimerization; D004337:Drug Carriers; D016503:Drug Delivery Systems; D007275:Injections, Intravenous; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D011092:Polyethylene Glycols; D014640:Vancomycin