Differential influence of anionic and cationic charge on the ability of amphiphilic drugs to interact with DPPC-liposomes.
The compounds clofibric acid and chlorphentermine have identical aromatic ring systems, but when charged their side chains are anionic or cationic, respectively. The drugs were applied as tools to investigate whether the interaction of amphiphilic drugs with the zwitterionic dipalmitoyl-phosphatidylcholine (DPPC) depends on the charge of the polar side chain. In suspensions of DPPC-liposomes, the drug-effect on the phase-transition temperature (Tt) was evaluated by means of differential scanning calorimetry. The drug-binding was determined spectrophotometrically. The clofibric acid anion had a much weaker depressing effect on Tt than the chlorphentermine-cation and a considerably lower ability to bind to the DPPC-liposomes. Furthermore, a plot of the effect versus the binding suggested that the clofibric acid-anion had a lower intrinsic activity to reduce Tt compared with the chlorphentermine-cation. In contrast, when the dissociation-equilibrium was shifted towards the uncharged state both drugs were indistinguishable with respect to effect and binding, suggesting that the differences observed with the charged forms could indeed be attributed to the opposite charges. The findings are tentatively explained to result from a different ability of the anionic and the cationic form to reach the hydrophobic interior of the DPPC-bilayer.
Mohr
K
K
Department of Pharmacology, University of Kiel, Federal Republic of Germany.
Struve
M
M
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism*; D000838:Anions; D002152:Calorimetry, Differential Scanning; D002412:Cations; D002745:Chlorphentermine / Q000378:metabolism; D002995:Clofibric Acid / Q000378:metabolism; D004337:Drug Carriers; D004347:Drug Interactions; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D013053:Spectrophotometry
D000838:Anions; D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D004364:Pharmaceutical Preparations; D015060:1,2-Dipalmitoylphosphatidylcholine; D002995:Clofibric Acid; D002745:Chlorphentermine