Evaluation of the Interaction of Propranolol with 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) Liposomes: The Langmuir Model

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• 作者：Pieter Saveyn ; Jan Cocquyt ; Marcel De Cuyper ; Paul Van der Meeren
• 刊名：Langmuir
• 出版年：2008
• 出版时间：June 17, 2008
• 年：2008
• 卷：24
• 期：12
• 页码：6007 - 6012
• 全文大小：139K
• 年卷期：v.24,no.12(June 17, 2008)
• ISSN：1520-5827

文摘

The interaction of the amine containing β-receptor blocking agent propranolol (Ppn) with dimyristoylphosphatidylcholine (DMPC) vesicles was studied. Using a centrifugation assay, the protonated as well as unprotonated amount of the drug sorbed was verified, whereas the binding of the protonated Ppn was deduced from the surface charge density of the vesicles as calculated from electrophoretic mobility measurements. Assuming a 1:1 binding, a Langmuir model with only two parameters was found to be sufficient to fit all experimental data. Sensitivity analysis revealed that the estimated values of these parameters were reliable and independent from each other. These parameters were truly intrinsic, as electrostatic interactions were accounted for in the model. It was found that the pK_a of Ppn shifted from 9.24, when disolved in water, downward by 1.34 units upon sorption, indicating that the intrinsic partition coefficient of the unprotonated Ppn was about 22 times higher than that of the protonated analog. In addition, a significant increase in the affinity of both Ppn analogs with increasing salt concentration was found. Theoretical analysis revealed that the Langmuir sorption model may be considered as a partitioning model with decreasing partition coefficient as the sorbed amount increases. Thus, the Langmuir model provides a better fit than a simple partition model at conditions that induce a substantial amount of propranolol sorbed, such as high pH and high propranolol concentrations.