Design and characterization of liposomes containing long-chain N-AcylPEs for brain delivery: Penetration of liposomes incorporating GM(1) into the rat brain

Purpose. To develop a suitable liposomal carrier to encapsulate neuroactive compounds that are stable enough to carry them to the brain across the blood-brain barrier with the appropriate surface characteristics for an effective targeting and for an active membrane transport. Methods. Liposomes containing glycosides and a fusogenic lipid were prepared by extrusion. Photon correlation spectroscopy, fluorescence spectroscopy, and differential scanning calorimetry were used to characterize liposomal preparations. Tissue distribution was determined by using 3H-cholesterylhexadecylether as a marker. Results. The incorporation of glycoside determinants and N-palmitoylphosphatidylethanolamine gives liposomes with similar initial size, trapped volume, negative surface charge, bilayer fluidity, and melting temperature, except for monosialoganglioside-containing liposomes, which showed less negative surface charge and the highest size, trapped volume and melting temperature. All glycosilated formulations gave liposomes able to retain up to the 95% of encapsulated carboxyfluorescein after 90 min at physiologic temperature even in the presence of serum. Monosialoganglioside liposomes were recovered in the cortex, basal ganglia, and mesencephalon of both brain hemispheres. The liver uptake was higher for sulfatide- and glucose-liposomes, whereas the higher blood levels were observed for glucose- and mannose-liposomes. Conclusions. These results show the suitability of such liposomal formulations to hold encapsulated drugs. Moreover, the brain uptake of monosialoganglioside liposomes makes them good candidates as drug delivery systems to the brain.