title: Evaluation of the interaction of propranolol with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes: the Langmuir model.
abstract: The interaction of the amine containing beta-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 pKa of Ppn shifted from 9.24, when dissolved 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.
authors.affiliation: Particle and Interfacial Technology Group, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Gent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Saveyn
authors.forename: Jan
authors.initials: J
authors.lastname: Cocquyt
authors.forename: Marcel
authors.initials: M
authors.lastname: De Cuyper
authors.forename: Paul
authors.initials: P
authors.lastname: Van der Meeren
mesh_terms: D000327:Adsorption; D002627:Chemistry, Physical / Q000379:methods; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D004563:Electrochemistry / Q000379:methods; D004586:Electrophoresis; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry*; D008956:Models, Chemical; D011189:Potassium Chloride / Q000737:chemistry; D011433:Propranolol / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D008081:Liposomes; D014867:Water; D011189:Potassium Chloride; D011433:Propranolol; D004134:Dimyristoylphosphatidylcholine