efficacy of chemotherapy due to changes in pharmacokinet-Many drugs are successfully loaded into preformed liposomes ics and biodistribution of the encapsulated drug and are by using various gradients and transmembrane potential. Several therefore widely used as a drug delivery system (5). One experimental breakthroughs, however, have not been paralleled of the main problems in their use in chemotherapy is efficient by theoretical understanding of the processes. Recently, we have and stable encapsulation of drug molecules.
developed a rigorous treatment of loading of weak acids and bases
In the past two decades a number of methods for loading into liposomes. The model is based on equilibration of chemical of ions ( 6) and drugs into the liposomes, based on pH gradipotentials of permeable neutral species. Charged molecules are ent (7) and ammonium salt gradient (8-10) were developed not allowed to permeate the membrane. Although this assumption is quite reasonable and experimental data fit the theoretical predic-to optimize drug loading into vesicles (11). In parallel, diftions rather well, we have extended the model of liposome loading. ferent physicochemical methods for measuring loading effi-In the expanded model, terms which allow leakage of protons, cacy, pH transmembrane gradient, and transmembrane pobuildup of the transmembrane pH gradient, an antiport exchange tential have been established (4, 12, 13). of various cations with protons, and leakage of other molecules Recently we have developed a rigorous treatment of drug from or into liposomes are added to the basic model. ᭧ 1997 Academic influx and efflux into vesicles. In this model we have as-Press sumed that only neutral molecules can permeate the bilayer