A novel method for high-yield entrapment of solutes into small liposomes

摘要

Formulation of drugs in liposomes can be optimized in terms of drug content, vesicle stability in the biological milieu and biodistribution profile by tailoring vesicle characteristics. For instance, liposomal size determines the extent of vesicle uptake by the reticuloendothelial system (RES), depending on the route of administration. Thus, avoidance of the RES after intravenous injection of liposomes destined for alternative cell target requires small (<200 nm diameter) vesicle size. A small size is also required for the access to and uptake of vesicles by the regional lymph nodes after subcuuaneous injection. Unfortunately however, entrapment of drugs by classical methods into liposomes of small size is minimal, especially with methods applicable to a wide spectrum of drugs. On the other hand, high yield entrapment of drugs by the dehydration-rehydration procedure generates large, micrometer size liposomes. Here we report a modification of the latter method in which dehydration of preformed empty small vesicles in the presence of sucrose and the solute destined for entrapment leads, on subsequent rehydration, to the formation of smaller vesicles exhibiting high entrapment vaues.