New pH-Sensitive Liposomes Using Bis(6-hemisuccinyloxyhexyl) Fumarate

摘要

In order to develop pH-sensitive liposomes that are stable in plasma, liposomes containing membrane-spanning bipolar amphiphiles as protonatable components were studied. Sonicated small unilamellar liposomes composed of dioleoylphosphatidylethanolamine (DOPE), dioleoylphosphatidylcholine (DOPC) and bis(6-hemisuccinyloxyhexyl) fumarate (BHF) in a 3 : 1 : 1 molar ratio are stable at neutral pH, but destabilized at weakly acidic pH with 50% leakage of entrapped materials at about pH 5.5. The liposomes are relatively stable in plasma such that only a few percent entrapped calcein was released in 50% plasma within 1.5 h incubation at 37 ∩, while about 10% entrapped calcein was released from sonicated liposomes composed of DOPE , DOPC, and oleic acid (OA) in a 3 : 1 : 1 molar ratio under the identical conditions. The aqueous contents mixing and lipid components mixing experiments suggest that the protonation of BHF may induce fusion between the liposomes, followed by the release of the entrapped materials.