FLUORINATED PHOSPHATIDYLCHOLINE-BASED LIPOSOMES - H+ NA+ PERMEABILITY, ACTIVE DOXORUBICIN ENCAPSULATION AND STABILITY IN HUMAN SERUM/

The active encapsulation of doxorubicin (DOX) into fluorinated liposom es, the stability of these liposomes with respect to encapsulated DOX release in buffer and in human serum, and their H+/Na+ membrane permea bility have been investigated and compared to those of their conventio nal hydrogenated analogues. These fluorinated liposomes are made from highly fluorinated phosphatidylcholines and contain a fluorinated core whithin their membrane. We found that the presence of this fluorinate d core is not a barrier for the active encapsulation of DOX. Efficient (> 90%) and stable loading could be achieved using a transmembrane am monium sulfate or even, in the absence of Na+, a transmembrane pH grad ient. The higher H+/Na+ permeability found for the fluorinated membran es, as compared to conventional ones, is responsible for the lower sta bility observed for the DOX-loaded fluorinated liposomes when incubate d in a physiological buffer (PBS) or in human serum. It is also notice able that the retention of DOX is increased in human serum and for the liposomes whose membranes are in a gel or in a semi-fluid semi-gel st ate at 37 degrees C.