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.