PERMEABILITY AND STABILITY IN BUFFER AND IN HUMAN SERUM OF FLUORINATED PHOSPHOLIPID-BASED LIPOSOMES

The stability (with respect to encapsulated carboxyfluorescein release ) of fluorinated liposomes and their membrane permeability have been i nvestigated in buffer and in human serum as compared to conventional h ydrogenated analogues. These fluorinated liposomes are made from highl y fluorinated phosphatidylcholines and contain a fluorinated core whit hin their membrane. In buffer and in their fluid state, the fluorinate d liposomes retain much more efficiently their entrapped content and d isplay lower membrane permeability coefficients than any of their hydr ogenated counterparts. This indicates that the fluorinated core acts a s a very efficient barrier to permeation. In terms of molecular struct ure/permeability relationships, the thicker the fluorinated lipophobic core, the more efficient the barrier to permeation. In their gel stat e, the fluorinated core has, however, almost no effect on permeation. Interestingly, some of the 'fluid' fluorinated liposomes were even les s permeable than 'gel' or 'gel-like' ones, including egg phosphatidylc holines/cholesterol liposomes. Human serum destabilizes the 'fluid' fl uorinated liposomes but to a lesser extent than the 'fluid' hydrogenat ed ones, indicating that the fluorinated lipophobic core inside the li posomal membrane protects the vesicles, possibly by reducing their int eractions with serum components. 'Gel' or 'gel-like' fluorinated lipos omes are significantly more stable in serum than in buffer. They art a lso more stable than conventional 'gel' or 'gel-like' liposomes.