Modification of liposomes composed of a cationic lipid TMAG and an anionic lipid DSPG with a PEGylated lipid based on the investigation of lipid structures
Modification of liposomes composed of a cationic lipid TMAG and an anionic lipid DSPG with a PEGylated lipid based on the investigation of lipid structures
复制标题
DOI：
10.1016/j.colsurfa.2022.130891
复制
发表时间：
2022-12
期刊：
影响因子：
--
通讯作者：
Miyuki Hohokabe;Kenjirou Higashi;Yurina Yamada;Taiki Fujimoto;Taisei Tokumoto;H. Imamura;T. Morita;Keisuke Ueda;W. Limwikrant;K. Moribe
中科院分区：
文献类型：
--
作者：
Miyuki Hohokabe;Kenjirou Higashi;Yurina Yamada;Taiki Fujimoto;Taisei Tokumoto;H. Imamura;T. Morita;Keisuke Ueda;W. Limwikrant;K. Moribe
荷电脂质体作为功能性脂质体被广泛应用于药物的控制释放和靶向性研究。本研究采用水合法和挤出法制备了阳离子脂质N-（α-三甲基氨乙酰基）-二硬脂酰-D-谷氨酸盐（TMAG）和阴离子脂质1，2-双十八酰-sn-甘油-3-磷酸-1 ′-外消旋-甘油（DSPG）的脂质体，TMAG/DSPG的摩尔比为0：10-10：0。小角X射线散射（SAXS）研究表明，TMAG和DSPG形成了层状结构。除5：5和6：4组成的脂质体外，脂质体薄膜形成的脂质体大小约为100 nm，可将核黄素包裹在内水相中。组成为0：10-4：6的脂质体的zeta电位均为负电荷，而组成为7：3-10：0的脂质体的zeta电位均为正电荷。当组成从0：10或10：0接近5：5时，脂双层从液晶相到凝胶相的相变温度升高，荧光各向异性程度增加。因此，等摩尔混合物周围的脂质双层可以形成具有低脂烷基链流动性的刚性结构。相反的离子头基和刚性脂质双层的较小曲率的表面电荷抵消应防止脂质体形成在5：5和6：4的组成。然而，5：5的等摩尔组成可以通过将二硬脂酰磷脂酰乙醇胺-聚乙二醇2000（DSPE-PEG 2000）以4%的摩尔比修饰到脂质双层中而形成脂质体，因为它可以降低脂质双层的刚性，为脂质双层提供正曲率，并且通过空间位阻稳定脂质体在水中的分散。
Charged lipids are widely utilized in functional liposomes for controlled release and targeting of drugs. In this study, we prepared the liposomes composed of a cationic lipidN-(α-trimethylammonioacetyl)-distearoyl-D-glutamate chloride (TMAG) and an anionic lipid 1,2-dioctadecanoyl-sn-glycero-3-phospho-1′-rac-glycerol (DSPG) with the molar ratio of TMAG/DSPG = 0:10–10:0 by hydration and extrusion methods. SAXS study for the lipid thin films revealed the formation of lamellar structures of TMAG and DSPG. The lipid thin film, except for the composition of 5:5 and 6:4, formed a liposome with a size of ∼100 nm that could encapsulate riboflavin in the inner aqueous phase. The zeta potentials of liposomes with the composition of 0:10–4:6 showed negative charges, while those of 7:3–10:0 showed positive charges. As the composition approached from 0:10 or 10:0 to 5:5, the phase transition temperature of the lipid bilayer from liquid crystalline phase to gel phase became higher, and the extent of fluorescence anisotropy increased. Thus, the lipid bilayer around the equimolar mixture could form a rigid structure with low fluidity of lipid alkyl chains. The surface charge cancellation by the opposite ionic head groups and the less curvature of the rigid lipid bilayer should prevent the liposomal formation at the composition of 5:5 and 6:4. However, the equimolar composition of 5:5 could form a liposome by the modification of distearoylphosphatidylethanolamine-polyethyleneglycol 2000 (DSPE-PEG2000) into the lipid bilayer at the molar ratio of 4% because it can reduce the rigidity of the lipid bilayer, provide positive curvature to the lipid bilayer, and stabilize the liposome dispersion in water through steric hindrance.