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.