Effects of charged drugs on the phase transition temperatures of phospholipid bilayers.

An approach is presented which allows the description of drug binding to lipid bilayers, when the drug is present in both charged and uncharged forms. Binding is described by Langmuir adsorption isotherms, with the maximum number of binding sites being 1/60 A2. An estimate of the change in drug pK on binding is necessary, and is close to zero for most drugs binding to dipalmitoyl phosphatidylcholine, although delta pK = 1.0 for procaine. From the binding curves it is possible to calculate the drug-induced decreases in lipid phase transition temperature, assuming ideal behaviour. Good fits between experiment and theory are possible, giving values for the dissociation constant describing drug binding to the membrane.