Preparation of liposomes, lipid nanoparticles, or polymer nanoparticles by nanoprecipitation and their purification: Where are membrane processes?

Nanoprecipitation is a key method to prepare colloids such as liposomes, lipid and polymer nanoparticles. Obtaining a final formulation requires three main steps, the first one consists in mixing the aqueous and organic phases, the solute to be precipitated being added to one of the two phases, according to its solubility. In a second step, the colloidal suspension obtained is concentrated and diafiltrated with an appropriate buffer to remove the solvent required for nanoprecipitation. The last step is sterilization of the resulting concentrated and diafiltrated colloidal suspension. Membrane processes can be used during the three stages. First, a membrane is an option for mixing both phases, although classical micromixers are generally preferred. Tangential flow filtration is used for concentration and diafiltration of the colloidal suspension obtained by nanoprecipitation. Finally, sterile filtration removes potential contaminants before the final use of the colloidal suspension in the delivery of active principle(s). In the following, principles and applications of these three membrane processes are presented and their advantages, limits and some perspectives are discussed.