Habib M J, Akogyeram C O, Ngofa E N, Biswas M, Betageri G V
College of Pharmacy, Howard University, Washington, DC 20059.
Membr Biochem. 1993 Jul-Sep;10(3):145-54. doi: 10.3109/09687689309150261.
The solubilization of multilamellar liposomes by metoprolol tartrate (MPL) has been studied as a function of pH, [MPL], [dimyristoylphosphatidylcholine (DMPC)], temperature and lipid composition. The solubilization of liposomes at 37 degrees C by 7.3 nM MPL occurred at different rates at different pH values. MPL completely solubilized by 7.2 mM DMPC liposomes after about 17 h at pH 12, but only a partial solubilization occurred at pH 10 and 11. Between pH 7 and 9 no change in turbidity was observed after 1 week. Addition of cholesterol (CHOL) to DMPC (2:1 mol) had very little effect on solubilization after 24 h, however with DMPC:CHOL (5:1 mol) the decrease in turbidity was observed after 24 h, even though solubilization was much less compared with that of DMPC alone. The rate of solubilization was decreased when dipalmitoylphosphatidylcholine liposomes were employed. Addition of dicetylphosphate (DCP) to DMPC liposomes reduced the rate of solubilization significantly. The solubilization of liposomes by 7.3 mM MPL as a function of [DMPC], indicated that the lower the liposome concentration the greater the effect on solubilization. It is concluded that MPL in the non-ionized form has a solubilizing effect on liposomes, and addition of CHOL or DCP to DMPC has a stabilizing effect against solubilization.
已研究了酒石酸美托洛尔（MPL）对多层脂质体的增溶作用，该作用是pH、[MPL]、[二肉豆蔻酰磷脂酰胆碱（DMPC）]、温度和脂质组成的函数。在37℃下，7.3 nM MPL对脂质体的增溶在不同pH值下速率不同。在pH 12时，7.2 mM DMPC脂质体在约17小时后被MPL完全增溶，但在pH 10和11时仅发生部分增溶。在pH 7至9之间，1周后未观察到浊度变化。向DMPC（2:1摩尔比）中添加胆固醇（CHOL）在24小时后对增溶作用影响很小，然而对于DMPC:CHOL（5:1摩尔比），24小时后观察到浊度降低，尽管与单独的DMPC相比增溶作用要小得多。当使用二棕榈酰磷脂酰胆碱脂质体时，增溶速率降低。向DMPC脂质体中添加十六烷基磷酸酯（DCP）显著降低了增溶速率。7.3 mM MPL对脂质体的增溶作用作为[DMPC]的函数表明，脂质体浓度越低，对增溶的影响越大。得出的结论是，非离子形式的MPL对脂质体有增溶作用，向DMPC中添加CHOL或DCP对增溶有稳定作用。
