NOVEL LIPOSOME SYSTEMS BASED ON THE INCORPORATION OF (PERFLUOROALKYL)ALKENES (FMHNE) INTO THE BILAYER OF PHOSPHOLIPID LIPOSOMES

Simultaneous dispersion in water of dimyristoylphosphatidyl choline (D MPC) and a linear (perfluoroalkyl)alkene (FmHnE) with a CmF2m+1CH=CHCn H2n+1 structure results in the incorporation of the (perfluoroalkyl)al kene into the DMPC liposome bilayer to form ''fluorinated'' liposomes, i.e. liposomes containing an internal fluorinated core within the lip id bilayer. In the case of F4H10E, it was found that the formation of DMPC: F4H10E (1:1 mole ratio) small unilamellar vesicles (SUVs), 19 nm in diameter, was favored over other structures, independently of the initial 1:1 or 1:2 (DMPC:F4H10E mole ratio) formulation. The incorpora tion of the (perfluoroalkyl)alkene into the liposome bilayer resulted in marked changes in the physicochemical properties of the system. The stability of the mixed DMPC: FmHnE liposomes to particle coarsening w ith respect to time at 25-degrees-C was significantly increased with r espect to DMPC-only liposomes. A lowering of the liposomes' gel-to-liq uid crystal phase transition temperatures was measured by steady state fluorescence anisotropy. Measurements of the liposome membrane permea bility in an aqueous buffer and human serum were made for the fluoresc ent marker carboxyfluorescein. The incorporation of all the FmHnE comp ounds tested significantly increased the encapsulation stability for t he entrapped molecules with respect to the reference DMPC system in bu ffer. The presence of the compound F4H10 resulted in the greatest enca psulation stability, the encapsulation half-life t1/2 being 16 times l onger than that of the DMPC liposome reference. This compound also had a stabilizing effect when tested in human serum. However, differences in the encapsulation stability were not significant between liposomes composed of DMPC/cholesterol/F4H10E when compared with the reference DMPC/cholesterol in serum.