g(m1)-ganglioside and 1-palmitoylphosphatidylethanolamine

To develop a suitable liposomal carrier to encapsulate neu roactive compounds that are stable enough to carry them to the brain across the blood-brain barrier with the appropriate surface characteri tics for an effective targeting and for an active membrane transport.. Liposomes containing glycosides and a fusogenic lipid were prepared by extrusion. Photon correlation spectroscopy, fluorescent spectroscopy, and differential scanning calorimetry were used to characterize liposomal preparations. Tissue distribution was determined by using 3H-cholesterylhexadecylether as a marker.. The incorporation of glycoside determinants and N-palmitoylphosphatidylethanolamine gives liposomes with similar in tial size, trapped volume, negative surface charge, bilayer fluidity, and melting temperature, except for monosialoganglioside-containing liposomes, which showed less negative surface charge and the highe 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.. 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.

Topics: Animals; Blood-Brain Barrier; Brain; Drug Delivery Systems; Drug Design; G(M1) Ganglioside; Liposomes; Lysophospholipids; Male; Rats; Rats, Sprague-Dawley

Liposomes containing negatively-charged phospholipid, N-palmitoylphosphatidylethanolamine (NPPE) were examined for stability in the presence of human serum, using the release of the entrapped 5,6-carboxyfluorescein as an aqueous marker. Either small unilamellar vesicles (SUV) or large unilamellar vesicles (LUV) were used. Incorporation of NPPE into PC SUV decreases leakage in the presence of serum or phosphate-buffered saline, no strictly related to size increase observed and to the surface negative charge present. The stabilizing effect of NPPE and Chol were synergistic. Inhibition of destabilization induced by serum of PC/Chol liposomes was observed when NPPE concentrations were above 12 mol%. Change in the membrane fluidity or incorporation of a monosialoganglioside into liposomes do not significantly change the half-life of liposomes in the presence of a high NPPE concentration. Incorporation of NPPE into PC/Chol liposomes increases membrane rigidity which does not change after serum incubation. The presence of NPPE in liposomes decreases lipid transfer/exchange between liposomes and lipoproteins although the same amount of serum proteins were incorporated as in PC/Chol liposomes. As expected, these proteins are accessible to trypsin digestion. In accordance with these results, the liposome agglutination assay shows no steric barrier activity. As a whole, the results obtained in this paper suggest a complex mechanism for stabilization of NPPE containing liposomes in human serum.

Topics: Blood; Blood Proteins; Cholesterol; Drug Stability; Drug Synergism; Electrochemistry; G(M1) Ganglioside; Gangliosides; Half-Life; Humans; Lipids; Liposomes; Lysophospholipids; Membrane Fluidity; Phosphatidylcholines; Phosphatidylserines; Photons; Spectrum Analysis; Trypsin