ABSTRACT
Great interest in lipid conjugates with polyethylene glycol (PEG)* was generated recently as a result of the discovery that incorporation of PEG-lipids into liposomes yields preparations with superior therapeutic performance as compared to conventional liposomes. 1 Such liposomes remain in blood circulation for extended periods of time (t112 ~ 48 h in humans) and distribute through an organism relatively evenly with most of the dose remaining in the blood compartment and only 10 to 15% of the dose ending up in liver. This constitutes a significant improvement over conventional liposomes; typically over 90% of conventional liposomes end up in liver within a few hours from injection (for a comprehensive review of the subject see Reference 2). Despite a great deal of activity generated in the field of PEG-grafted liposomes hardly any attention was paid to the chemistry of the conjugation processes and to the chemical properties of various PEG-lipids and their relationship to the properties of the corresponding liposomes. This chapter will attempt to fill the gap by reviewing these chemical aspects of the field.
