Evaluation of the interaction of propranolol with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes : the Langmuir model
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 P...
| Veröffentlicht in: | Langmuir : the ACS journal of surfaces and colloids. - 1992. - 24(2008), 12 vom: 17. Juni, Seite 6007-12 |
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| Weitere Verfasser: | , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2008
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| Zugriff auf das übergeordnete Werk: | Langmuir : the ACS journal of surfaces and colloids |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Liposomes Water 059QF0KO0R Potassium Chloride 660YQ98I10 Propranolol 9Y8NXQ24VQ Dimyristoylphosphatidylcholine |
| Zusammenfassung: | 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 |
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| Beschreibung: | Date Completed 04.08.2008 Date Revised 21.11.2013 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1520-5827 |
| DOI: | 10.1021/la800025y |