pH-sensitive PEG lipids containing orthoester linkers: new potential tools for nonviral gene delivery.

The synthesis and properties of pH-sensitive polyethylene glycol (PEG) lipids are described. The sensitivity of these conjugates to slightly acidic pH was clearly related to the structure of the orthoester linkage involved. It was found that pH-sensitive PEG lipids stabilized cationic lipid/DNA isoelectric complexes as efficiently as their non-pH-sensitive PEG analogs at neutral pH.