Novel liposome systems based on the incorporation of (perfluoroalkyl) alkenes (F mH nE) into the bilayer of phospholipid liposomes

Simultaneous dispersion in water of dimyristoylphosphatidyl choline (DMPC) and a linear (perfluoroalkyl)alkene (F mH nE) with a C mF 2m+1CHCHC nH 2n+1 structure results in the incorporation of the (perfluoroalkyl)alkene into the DMPC liposome bilayer to form “fluorinated” liposomes, i.e. liposomes containing an internal fluorinated core within the lipid 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 incorporation 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: F mH nE liposomes to particle coarsening with respect to time at 25°C was significantly increased with respect to DMPC-only liposomes. A lowering of the liposomes' gel-to-liquid crystal phase transition temperatures was measured by steady state fluorescence anisotropy. Measurements of the liposome membrane permeability in an aqueous buffer and human serum were made for the fluorescent marker carboxyfluorescein. The incorporation of all the F mH nE compounds tested significantly increased the encapsulation stability for the entrapped molecules with respect to the reference DMPC system in buffer. The presence of the compound F4H10E resulted in the greatest encapsulation stability, the encapsulation half-life t 1 2 being 16 times longer 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.