Kirby C, Clarke J, Gregoriadis G
Biochem J. 1980 Feb 15;186(2):591-8. doi: 10.1042/bj1860591.
Small unilamellar neutral, negatively and positively charged liposomes composed of egg phosphatidylcholine, various amounts of cholesterol and, when appropriate, phosphatidic acid or stearylamine and containing 6-carboxyfluorescein were injected into mice, incubated with mouse whole blood, plasma or serum or stored at 4 degrees C. Liposomal stability, i.e. the extent to which 6-carboxyfluorescein is retained by liposomes, was dependent on their cholesterol content. (1) Cholesterol-rich (egg phosphatidylcholine/cholesterol, 7:7 molar ratio) liposomes, regardless of surface charge, remained stable in the blood of intravenously injected animals for up to at least 400min. In addition, stability of cholesterol-rich liposomes was largely maintained in vitro in the presence of whole blood, plasma or serum for at least 90min. (2) Cholesterol-poor (egg phosphatidylcholine/cholesterol, 7:2 molar ratio) or cholesterol-free (egg phosphatidylcholine) liposomes lost very rapidly (at most within 2min) much of their stability after intravenous injection or upon contact with whole blood, plasma or serum. Whole blood and to some extent plasma were less detrimental to stability than was serum. (3) After intraperitoneal injection, neutral cholesterol-rich liposomes survived in the peritoneal cavity to enter the blood circulation in their intact form. Liposomes injected intramuscularly also entered the circulation, although with somewhat diminished stability. (4) Stability of neutral and negatively charged cholesterol-rich liposomes stored at 4 degrees C was maintained for several days, and by 53 days it had declined only moderately. Stored liposomes retained their unilamellar structure and their ability to remain stable in the blood after intravenous injection. (5) Control of liposomal stability by adjusting their cholesterol content may help in the design of liposomes for effective use in biological systems in vivo and in vitro.
将由鸡蛋磷脂酰胆碱、不同量胆固醇以及在适当情况下的磷脂酸或硬脂胺组成、含有6-羧基荧光素的小单层中性、带负电荷和带正电荷的脂质体注射到小鼠体内，与小鼠全血、血浆或血清一起孵育，或在4℃下储存。脂质体稳定性，即6-羧基荧光素被脂质体保留的程度，取决于其胆固醇含量。（1）富含胆固醇的（鸡蛋磷脂酰胆碱/胆固醇，摩尔比7:7）脂质体，无论表面电荷如何，在静脉注射动物的血液中至少保持稳定达400分钟。此外，富含胆固醇的脂质体在全血、血浆或血清存在下于体外至少90分钟内基本保持稳定性。（2）胆固醇含量低的（鸡蛋磷脂酰胆碱/胆固醇，摩尔比7:2）或无胆固醇的（鸡蛋磷脂酰胆碱）脂质体在静脉注射后或与全血、血浆或血清接触后很快（最多在2分钟内）失去大部分稳定性。全血以及在一定程度上血浆对稳定性的损害小于血清。（3）腹腔注射后，富含胆固醇的中性脂质体在腹腔内存活并以完整形式进入血液循环。肌肉注射的脂质体也进入循环，尽管稳定性有所降低。（4）在4℃下储存的中性和带负电荷的富含胆固醇的脂质体的稳定性可维持数天，到53天时仅略有下降。储存的脂质体保持其单层结构以及静脉注射后在血液中保持稳定的能力。（5）通过调节胆固醇含量来控制脂质体稳定性可能有助于设计在体内和体外生物系统中有效使用的脂质体。
