Krämer S D, Braun A, Jakits-Deiser C, Wunderli-Allenspach H
Biopharmacy, Department of Pharmacy, ETH Zürich, Switzerland.
Pharm Res. 1998 May;15(5):739-44. doi: 10.1023/a:1011923103938.
Prediction of the pH-dependent affinity of (RS)-[3H]propranolol to mixed phosphatidylcholine (PhC)/phosphatidylinositol(Phl) membranes from the partitioning in the single lipid liposome/buffer systems.
Partition studies in liposome/buffer systems were performed by means of equilibrium dialysis at 37 degrees C between pH 2 and 11 at a molar propranolol to lipid ratio of 10(-6) to 10(-5) in the membrane. Results. The Phl membrane more strongly attracts the protonated (RS)-[3H]propranolol than the neutral solute, i.e. the partition coefficient of the protonated base (Pi) is 17'430+/-1320, P of the neutral compound (Pn) is 3110+/-1650. In the PhC-liposome system Pi is 580+/-17, Pn 1860+/-20. The partition coefficients show an exponential dependence on the molar Phl fraction in mixed liposomes. The partitioning in mixed PhC/Phl membranes is predictable from Pn and Pi in the single lipid liposome systems.
The negative charge of biological lipid membranes causes strong electrostatic interactions with positively charged solutes. This strong attraction is not predictable from the octanol/buffer partition system, but it is important regarding drug accumulation in the tissue and drug attraction by certain lipids in the vicinity of membrane proteins.
通过（RS）-[3H]普萘洛尔在单一脂质脂质体/缓冲液系统中的分配情况，预测其对混合磷脂酰胆碱（PhC）/磷脂酰肌醇（Phl）膜的pH依赖性亲和力。
在37℃下，通过平衡透析法在pH 2至11之间进行脂质体/缓冲液系统中的分配研究，膜中普萘洛尔与脂质的摩尔比为10^(-6)至10^(-5)。结果。与中性溶质相比，Phl膜更强烈地吸引质子化的（RS）-[3H]普萘洛尔，即质子化碱的分配系数（Pi）为17430±1320，中性化合物的分配系数（Pn）为3110±1650。在PhC脂质体系统中，Pi为580±17，Pn为1860±20。分配系数对混合脂质体中Phl摩尔分数呈指数依赖性。混合PhC/Phl膜中的分配情况可根据单一脂质脂质体系统中的Pn和Pi进行预测。
生物脂质膜的负电荷与带正电荷的溶质产生强烈的静电相互作用。这种强烈的吸引力无法从正辛醇/缓冲液分配系统中预测，但对于药物在组织中的积累以及膜蛋白附近某些脂质对药物的吸引而言很重要。
