Binding of propranolol and gentamicin to small unilamellar phospholipid vesicles. Contribution of ionic and...

Binding of propranolol and gentamicin to small unilamellar phospholipid vesicles having different surface charges was studied at pH 4.4 using an ultra-centrifugation method, and the results were analyzed by an equation describing the Langmuir adsorption isotherms. Gentamicin, a polycationic drug, bound to negatively-charged small unilamellar vesicles composed of 60% phosphatidylcholine and 40% of either phosphatidylinositol, phosphatidylglycerol or phosphatidylserine in a manner consistent with a single class of binding sites but did not bind at all to small unilamellar vesicles of phosphatidylcholine alone. In contrast, propranolol bound readily to both neutral and negatively-charged liposomes in a manner consistent with two types of binding sites. Based on the binding parameters calculated from replots, it is suggested that the high-affinity site is probably at the surface of the liposome and that ionic forces are primarily responsible for this binding. The low-affinity, high-capacity binding site for propranolol was demonstrated with both neutral and negatively-charged liposomes and appeared to be independent of the surface charge. Gentamicin, which is not hydrophobic, did not bind to the low-affinity site. It is hypothesized that hydrophobic interactions are the driving force for propranolol binding to the low-affinity site which may be the interior of the lipid bilayer.