Optimization of a supercritical assisted process for the production of liposomes for industrial applications

Liposomes are spherical vesicles made of a double lipidic layer that surrounds an inner aqueous core. Several methods for the preparation of liposomes have been developed in the last decades. However, these methods present drawbacks, such as low reproducibility, batch operations, low encapsulation efficiency of hydrophilic compounds, a difficult control of liposome size distribution and high solvent residue, hindering the real industrial potential of these drug delivery systems. Supercritical fluid (SCF) technologies have been proposed to overcome several limitations of conventional processes for the production of micronized particles carriers, coprecipitates and nanocomposite polymeric structures. Recently, some techniques based on the use of supercritical carbon dioxide have been proposed also for liposome production. However, these methods have still some limitations related to the control of liposome dimension and size distribution and also show very low encapsulation efficiency of hydrophilic drug. The major limitation of these processes, both conventional and supercritical, derives from the hydration step of the lipid layer. Indeed, during this step, only a part of the water used for hydration is actually entrapped into liposomes, resulting in a low overall encapsulation efficiency. Therefore, the objective of this Ph.D. thesis is to develop a novel technology assisted by supercritical carbon dioxide for the production of liposomes of controlled dimensions. The proposed technique was called Supercritical assisted Liposome formation (SuperLip); in this process, first water droplets are produced; then, they are rapidly covered by phospholipids... [edited by Author]