Fukunaga M, Miller M M, Hostetler K Y, Deftos L J
Endocrinology. 1984 Aug;115(2):757-61. doi: 10.1210/endo-115-2-757.
The hypocalcemic effect of liposomal-entrapped calcitonin (CT) was evaluated in rats. Salmon CT and human CT were entrapped in liposomes composed of egg phosphatidylcholine with or without an equimolar amount of cholesterol. The liposomes were separated by Sepharose 4B chromatography into fractions consisting of large multilamellar vesicles and small unilamellar vesicles. The incorporation of CT was monitored by counting [125I]CT and by specific RIA. Liposomal entrapment enhanced the hypocalcemic potency of parenterally administered salmon CT and human CT. After iv administration, the large multilamellar vesicles were more potent than small unilamellar vesicles in their hypocalcemic effect; cholesterol inclusion in the MLV liposome preparation prolonged the hypocalcemia. However, with im administration, the cholesterol-free liposomes were more potent than their cholesterol-containing counterparts regardless of size. These studies demonstrate that liposomal entrapment can be used to enhance the hypocalcemic potency of CT. It appears that both the size and composition of the liposome preparation are important in this effect, as is the route of administration. It may be possible to produce liposome-CT preparations with advantageous pharmacological characteristics.
在大鼠中评估了脂质体包裹的降钙素（CT）的降钙效应。鲑鱼降钙素和人降钙素被包裹在由蛋黄卵磷脂组成的脂质体中，其中有无等摩尔量的胆固醇。通过琼脂糖4B色谱法将脂质体分离成由大多层囊泡和小单层囊泡组成的级分。通过计数[125I] CT和特异性放射免疫分析监测CT的掺入。脂质体包裹增强了胃肠外给药的鲑鱼降钙素和人降钙素的降钙效力。静脉注射后，大多层囊泡在其降钙作用方面比小单层囊泡更有效；在多层囊泡脂质体制剂中加入胆固醇可延长低钙血症。然而，肌肉注射时，无论大小，不含胆固醇的脂质体比含胆固醇的脂质体更有效。这些研究表明，脂质体包裹可用于增强CT的降钙效力。脂质体制剂的大小和组成以及给药途径在这种效应中似乎都很重要。有可能生产出具有有利药理学特性的脂质体-CT制剂。
