A method of stably encapsulating a weak acid drug in liposomes, at a high concentration, is disclosed. The method employs a proton shuttle mechanism involving the salt of a weak acid to generate a higher inside/lower outside pH gradient. The weak acid compound accumulates in liposomes in response to this gradient, and may be retained in the liposomes by cation-promoted precipitation or low permeability across the liposome transmembrane barrier. Also disclosed is a reagent combination for practicing the method, and a liposome composition formed by the method.