Preparation and Drug Entrapment Properties of Asymmetric Liposomes Containing Cationic and Anionic Lipids
Preparation and Drug Entrapment Properties of Asymmetric Liposomes Containing Cationic and Anionic Lipids
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DOI：
10.1021/acs.langmuir.0c01968
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发表时间：
2020-10-27
期刊：
影响因子：
3.9
通讯作者：
London, Erwin
中科院分区：
文献类型：
--
作者：
Li, Bingchen;London, Erwin
我们开发了环糊精催化的脂质交换方法来制备具有不对称电荷分布的大单层囊泡（lws），即内外小叶的脂质具有不同的净电荷。luv含有两性离子脂质（磷脂酰胆碱）、胆固醇和各种阳离子脂质（o -乙基磷脂酰胆碱或二酰-3-三甲基丙烷）或阴离子脂质（磷脂酰甘油、磷脂酰丝氨酸或磷脂酸）的混合物。制备了具有多种脂质组合的对称和不对称luv。不对称luv含有阳离子或阴离子的外叶和带相反电荷或不带电荷的内叶。用两性、阴离子或阳离子小叶制备的对称luv的行为与不对称luv的行为进行了比较。脂质交换通过定量薄层色谱法证实，脂质不对称通过一种新的测定阳离子荧光探针与LW外叶结合的方法证实。对于对称型和非对称型luv，阳离子型药物阿霉素的包封程度受内小叶上的电荷控制，在阴离子型内小叶的囊泡中包封程度最大，泄漏速度最慢。这表明，有可能选择内小叶脂质，以最大限度地增加载药的脂质体，而不依赖于外小叶脂质的身份。这意味着也应该有可能独立地改变叶外脂质，例如，赋予脂质囊泡有利的生物利用度和生物分布特性。
We have developed cyclodextrin-catalyzed lipid exchange methods to prepare large unilamellar vesicles (L Ws) with asymmetric charge distributions, i.e., with different net charges on the lipids in the inner and outer leaflets. LUVs contained a mixture of a zwitterionic lipid (phosphatidylcholine), cholesterol, and various cationic lipids (O-ethyl phosphatidylcholine or dioleoyl-3-trimethylammonium propane) or anionic lipids (phosphatidylglycerol, phosphatidylserine, or phosphatidic acid). Symmetric and asymmetric LUVs with a wide variety of lipid combinations were prepared. The asymmetric LUVs contained cationic or anionic outer leaflets and inner leaflets that had either the opposite charge or were uncharged. The behavior of symmetric LUVs prepared with zwitterionic, anionic, or cationic leaflets was compared to those of asymmetric LUVs. Lipid exchange was confirmed by quantitative thin-layer chromatography, and lipid asymmetry by a novel assay measuring binding of a cationic fluorescent probe to the LW outer leaflet. For both symmetric and asymmetric LUVs, the level of entrapment of the cationic drug doxorubicin was controlled by the charge on the inner leaflet, with the greatest entrapment and slowest leakage in vesicles with an anionic inner leaflet. This shows that it is possible to choose inner leaflet lipids to maximize liposomal loading of charged drugs independently of the identity of outer-leaflet lipids. This implies that it should also be possible to independently vary outer-leaflet lipids to, for example, impart favorable bioavailability and biodistribution properties to lipid vesicles.