caa a22 4500 477125778 CHVBK 20180405111649.0 cr unu---uuuuu 170330e19970601xx s 000 0 eng 10.1023/A:1012175111401 doi (NATIONALLICENCE)springer-10.1023/A:1012175111401 Free Fatty Acids Cause pH-Dependent Changes in Drug-Lipid Membrane Interactions Around Physiological pH [Elektronische Daten] [Stefanie Krämer, Christina Jakits-Deiser, Heidi Wunderli-Allenspach] Purpose. The influence of oleic acid (OA) and phosphatidylethanolamine (PhE) as membrane constituents on the partition behavior of (RS)-[3H]propranolol between unilamellar liposomes and buffer was studied as a function of pH. Methods. Partition studies were performed by means of equilibrium dialysis at 37°C over a broad pH range at a molar propranolol to lipid ratio in the membrane of 10−6. Results. As compared to the standard phosphatidylcholine (PhC)-liposome/buffer partition system PhE and OA have an enhancing effect on the apparent partition coefficient (D) of (RS)-[3H]propranolol between pH 6 and 11. Data analysis with Henderson-Hasselbalch equations revealed that the neutral propranolol has a higher affinity to membranes containing net neutral charged PhE than to pure PhC-liposomes. Net negatively charged PhE seems to have no significant influence on the partitioning. Deprotonated OA caused an increase in the true partition coefficient (P) of the protonated propranolol. Neutral OA showed no influence on the partitioning. From the fit D vs pH curves and from zeta potential measurements of the liposomes the intrinsic pKa values of the membranous lipids were calculated as 7.5 to 7.8 for OA and 9.7 to 9.8 for PhE. Conclusions. Since the pKa of membranous OA is close to the physiological pH and D depends on the ionisation state of OA, small pH changes around the physiological pH may cause large differences in drug-lipid membrane interactions. Plenum Publishing Corporation, 1997 partitioning nationallicence liposome nationallicence propranolol nationallicence drug-lipid membrane interactions nationallicence free fatty acid nationallicence phosphatidylethanolamine nationallicence Krämer Stefanie Biopharmacy, Department of Pharmacy, ETH Zürich, 8057 Zürich, CH-, Switzerland aut Jakits-Deiser Christina Biopharmacy, Department of Pharmacy, ETH Zürich, 8057 Zürich, CH-, Switzerland aut Wunderli-Allenspach Heidi Biopharmacy, Department of Pharmacy, ETH Zürich, 8057 Zürich, CH-, Switzerland aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 827-832 0724-8741 14:6<827 1997 14 11095 https://doi.org/10.1023/A:1012175111401 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012175111401 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Krämer Stefanie Biopharmacy, Department of Pharmacy, ETH Zürich, 8057 Zürich, CH-, Switzerland aut NATIONALLICENCE 700 1- Jakits-Deiser Christina Biopharmacy, Department of Pharmacy, ETH Zürich, 8057 Zürich, CH-, Switzerland aut NATIONALLICENCE 700 1- Wunderli-Allenspach Heidi Biopharmacy, Department of Pharmacy, ETH Zürich, 8057 Zürich, CH-, Switzerland aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 827-832 0724-8741 14:6<827 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer