A RIGOROUS THEORY OF REMOTE LOADING OF DRUGS INTO LIPOSOMES - TRANSMEMBRANE POTENTIAL AND INDUCED PH-GRADIENT LOADING AND LEAKAGE OF LIPOSOMES

Many drugs are successfully loaded into preformed liposomes by using v arious gradients and transmembrane potential. Several experimental bre akthroughs, however, have not been paralleled by theoretical understan ding of the processes. Recently, we have developed a rigorous treatmen t of loading of weak acids and bases into liposomes. The model is base d on equilibration of chemical potentials of permeable neutral species . Charged molecules are not allowed to permeate the membrane. Although this assumption is quite reasonable and experimental data fit the the oretical predictions rather well, we have extended the model of liposo me loading. In the expanded model, terms which allow leakage of proton s, buildup of the transmembrane pH gradient, an antiport exchange of v arious cations with protons, and leakage of other molecules from or in to liposomes are added to the basic model. (C) 1997 Academic Press