Mora Margarita, Sagristá Maria-Luisa, Trombetta Domenico, Bonina Francesco P, De Pasquale Anna, Saija Antonella
Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Barcelona, Spain.
Pharm Res. 2002 Oct;19(10):1430-8. doi: 10.1023/a:1020440229102.
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.
开发一种合适的脂质体载体，用于包裹神经活性化合物，该载体要足够稳定，能够携带这些化合物穿过血脑屏障到达大脑，同时具有适当的表面特性以实现有效靶向和主动膜转运。
通过挤压制备含有糖苷和融合脂质的脂质体。采用光子相关光谱、荧光光谱和差示扫描量热法对脂质体制剂进行表征。以3H-胆固醇十六烷基醚为标记物测定组织分布。
糖苷决定簇和N-棕榈酰磷脂酰乙醇胺的掺入使脂质体具有相似的初始大小、包封体积、负表面电荷、双层流动性和熔化温度，但含单唾液酸神经节苷脂的脂质体表面负电荷较少，大小、包封体积和熔化温度较高。所有糖基化制剂制备的脂质体在生理温度下90分钟后，即使在有血清存在的情况下，仍能保留高达95%的包封羧基荧光素。单唾液酸神经节苷脂脂质体在两个脑半球的皮质、基底神经节和中脑均有发现。硫苷和葡萄糖脂质体在肝脏中的摄取较高，而葡萄糖和甘露糖脂质体在血液中的水平较高。
这些结果表明此类脂质体制剂适合容纳包封的药物。此外，单唾液酸神经节苷脂脂质体对大脑的摄取使其成为向大脑递送药物的良好候选物。
