An overview of liposome lyophilization and its future potential

摘要

Lyophilization is a promising approach to ensure the long-term stability of liposomes. After decades of studies in this field, different lyoprotective mechanisms, such as water replacement and vitrification models, have been proposed. Much progress has been made in developing highly stable liposomes after lyophilization based on optimization of formulation and process parameters. Here, this paper reviews the lyoprotective mechanisms, the parameters affecting the lyoprotective effect and the techniques used in a large number of studies. The parameters are discussed with regard to the following two aspects: (1) the formulation factors: the choice of drug, the lipid bilayer composition, vesicle size, selection of lyoprotectants, combination of lyoprotectants and additives, dry mass ratio of lyoprotectant to lipid, distribution of lyoprotectant on the two sides of lipid bilayers and others, which are the key factors determining the lyoprotective effect of freeze-dried liposomes. (2) The technological factors: freezing protocols, drying protocols, storage conditions and others, which are the extrinsic factors affecting the stability of freeze-dried cakes. Moreover, encapsulated solute/drug retention (ESR), gel-to-liquid crystalline phase transition temperature (Tm) and glass transition temperature (Tg) are selected as indicators to investigate the protective effect during this process. Finally, the major areas and future potential of research on lyophilized liposomes are highlighted.