Supercritical fluid methods: An alternative to conventional methods to prepare liposomes

Liposomes are used as nanovectors to encapsulate several active molecules with a prolongation of the drug effect, to target specific tissues or to reduce certain side effects. Innovative therapies using nanovectors have been developed and accepted for clinical trials, however their conventional methods of production suffer from drawbacks such as the use of large amounts of organic solvents, the small quantities produced and the many steps involved in the production that prevent the production at industrial scale. For several years, supercritical fluid-based preparation processes have been considered as a good alternative to conventional liposome preparation methods. A number of supercritical fluid processes allowing the liposome preparation are described depending on the role of the supercritical fluid with respect to the liposome raw materials. The supercritical fluid can act as a solvent or a cosolvent for the lipids material which are next put in contact with an aqueous solution before or during the depressurization. The supercritical fluid can also be used as an antisolvent to induce the formation of proliposomes which can be easily converted into liposomes by hydration. Finally the supercritical fluid can be used as a dispersing agent in order to finely disperse the lipid molecules into an aqueous medium. Several of these methods using supercritical fluids to produce liposomes are described in the literature. The aim of this review article is to summarize and classify the current supercritical fluid-based liposome preparation methods according to the function of the supercritical fluid within the process and compare them in terms of liposome's physicochemical properties, hydration methods, molecules that can be encapsulated, encapsulation efficiencies and the use or not of organic solvents.