LIPOSOMES WITH DETACHABLE POLYMER COATING - DESTABILIZATION AND FUSION OF DIOLEOYLPHOSPHATIDYLETHANOLAMINE VESICLES TRIGGERED BY CLEAVAGE OF SURFACE-GRAFTED POLY(ETHYLENE GLYCOL)

Plasma-stable liposomes (100 nn) were prepared from dioleoylphosphatid ylethanolamine (DOPE) and 3-6 mol% of a new disulfide-linked poly(ethy lene glycol)-phospholipid conjugate (mPEG-DTP-DSPE). In contrast to si milar preparations containing non-cleavable PEG-phospholipid conjugate , thiolytic cleavage of the grafted polymer chains facilitated rapid a nd complete release of the liposome contents. Furthermore, the detachm ent of PEG from DOPE liposomes resulted in liposomal fusion, Finally, while formulation of pH-sensitive DOPE/cholesterol hemisuccinate lipos omes with mPEG-DTP-DSPE abolished the pH sensitivity, cleavage of the PEG chains completely restored this property. These are the First exam ples of new useful properties of liposomes grafted with cleavable poly mer.