EFFECT OF THE CHOLESTEROL CONTENT OF SMALL UNILAMELLAR LIPOSOMES ON THEIR STABILITY INVIVO AND INVITRO
EFFECT OF THE CHOLESTEROL CONTENT OF SMALL UNILAMELLAR LIPOSOMES ON THEIR STABILITY INVIVO AND INVITRO
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DOI：
10.1042/bj1860591
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发表时间：
1980-01-01
影响因子：
4.1
通讯作者：
GREGORIADIS, G
中科院分区：
文献类型：
--
作者：
KIRBY, C;CLARKE, J;GREGORIADIS, G
有效利用脂质体作为药物载体的一个重要前提是控制其稳定性。将由卵磷脂酰胆碱、不同量的胆固醇和适当时的磷脂酸或硬脂胺组成并含有6-羧基荧光素的小单层中性、带负电和带正电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储存在4℃。 C. 脂质体稳定性，即脂质体保留 6-羧基荧光素的程度，取决于其胆固醇含量。富含胆固醇（鸡蛋磷脂酰胆碱/胆固醇，7:7摩尔比）的脂质体，无论表面电荷如何，在静脉注射的血液中保持稳定。注射动物至少 400 分钟。在全血、血浆或血清存在的情况下，富含胆固醇的脂质体的稳定性在体外基本上保持至少90分钟。低胆固醇（鸡蛋磷脂酰胆碱/胆固醇，摩尔比 7:2）或无胆固醇（鸡蛋磷脂酰胆碱）脂质体在静脉注射后很快（最多 2 分钟内）失去大部分稳定性。注射或接触全血、血浆或血清。全血和某种程度上血浆对稳定性的危害小于血清。 ip 之后注射后，富含中性胆固醇的脂质体在腹膜腔中存活，以完整的形式进入血液循环。肌内注射脂质体进入循环，但稳定性有所减弱。 4℃下储存的中性和带负电的富含胆固醇的脂质体的稳定性。 C 保持了几天，到 53 天时仅略有下降。储存的脂质体保留了其单层结构以及在静脉注射后在血液中保持稳定的能力。注射。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脂质体，以便在体内和体外生物系统中有效使用。
An important prerequisite for the effective use of liposomes as a drug carrier is control over their stability. 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.degree. C. Liposomal stability, i.e., the extent to which 6-carboxyfluorescein is retained by liposomes, was dependent on their cholesterol content. Cholesterol-rich (egg phosphatidylcholine/cholesterol, 7:7 molar ratio) liposomes, regardless of surface charge, remained stable in the blood of i.v. injected animals for up to at least 400 min. Stability of cholesterol-rich liposomes was largely maintained in vitro in the presence of whole blood, plasma or serum for at least 90 min. Cholesterol-poor (egg phosphatidylcholine/cholesterol, 7:2 molar ratio) or cholesterol-free (egg phosphatidylcholine) liposomes lost very rapidly (at most within 2 min) much of their stability after i.v. 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. After i.p. injection, neutral cholesterol-rich liposomes survived in the peritoneal cavity to enter the blood circulation in their intact form. Liposomes injected i.m. entered the circulation, but with somewhat diminished stability. Stability of neutral and negatively charged cholesterol-rich liposomes stored at 4.degree. 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 i.v. injection. 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.