Interactions of drugs with lipid membranes. Characteristics of liposomes containing polar or non-polar antitumur drugs
Interactions of drugs with lipid membranes. Characteristics of liposomes containing polar or non-polar antitumur drugs
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药物与脂质膜的相互作用。
DOI：
10.1016/0304-4165(79)90412-4
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发表时间：
1979
期刊：
影响因子：
--
通讯作者：
D. Stamp
中科院分区：
文献类型：
--
作者：
R. Juliano;D. Stamp
脂质体内包埋的极性药物存在于这些颗粒的内部水性隔室中，并且当脂质体膜被超声能量破裂时容易释放。非极性药物被发现或嵌入到脂质体膜中以及被发现在水性隔室中。非极性药物的嵌入部分相对难以被超声能量释放，极性和非极性药物从脂质体中的外排速率受脂质体膜的物理特性控制。因此，药物从合成磷脂酰胆碱组成的脂质体中流出，在脂质的相变温度下显示出最大速率。非极性药物从磷脂酰胆碱脂质体中的外排速率大于极性药物，非极性药物可以干扰合成磷脂酰胆碱的相变行为，极性药物则没有这种影响。因此，在非极性药物如硫酸长春碱和放线菌素D的存在下，二肉豆蔻酰磷脂酰胆碱的差示扫描量热法曲线显著改变，主峰变宽，在较低温度下出现第二峰。
Polar drugs entrapped within liposomes are found in the internal aqueous compartments of these particles, and are readily released when the liposome membrane is ruptured by ultrasonic energy. Non-polar drugs are found or intercalated into the liposome membrane as well as being found in the aqueous compartments. The intercalated fraction of the non-polar drug is relatively refractory to release by ultrasonic energy.The efflux rates of both polar adn non-polar drugs from liposomes are governed by the physical characteristics of the liposome membrane. Thus drug efflux from liposomes composed of synthetic phosphatidylcholines displays a maximal rate at the phase transition temperature of the lipid. The efflux rate of non-polar drugs from phosphatidylcholine liposomes is greater than that of polar drugs.Non-polar drugs can perturb the phase transition behavior of synthetic phosphatidylcholines; polar drugs have no such effect. Thus, in the presence of non-polar drugs such as vinblastine sulfate and actinomycin D, the differential scanning calorimetry profile of dimyristoylphosphatidylcholine is markedly altered, with a broadening of the major peak and the appearance of a second peak at lower temperature.