Enhancing the preservation of liposomes: The role of cryoprotectants, lipid formulations and freezing approaches

Post-Processing Techniques for the Improvement of Liposome Stability

“…According to the formulation of DCL2, where the drug was added to the organic phase whereas the inclusion complex was added to the aqueous phase of the liposome, this finding occurred because the presence of eugenol in the bilayer could interfere with the interaction between β-CD and the liposome; hence, leading to the rearrangement of the liposome structure [44]. In order to overcome the negative phenomena that occur during the freeze drying process of liposomes, adding a lyoprotectant to the liposome formulation has been extensively reported to inhibit vesicle aggregation, prevent the leakage of the encapsulated material and protect the phospholipid membrane from damage caused by ice crystals [41,42]. A variety of carbohydrates (monosaccharides, disaccharides, polysaccharides and synthetic saccharides), proteins (amino acids) and several alcohols that can interact with phospholipids could act as lyoprotectants (Table 2).…”

“…A variety of carbohydrates (monosaccharides, disaccharides, polysaccharides and synthetic saccharides), proteins (amino acids) and several alcohols that can interact with phospholipids could act as lyoprotectants (Table 2). To date, two lyoprotective mechanism-based disaccharides, the water replacement model and the vitrification model, have been proposed in the field of freeze-dried liposomes [41,42,45]. As shown in Figure 3, the former model explained the ability of sugar to replace water by interacting with phospholipids thereby maintaining the space between the phospholipid head groups (loose state) In order to overcome the negative phenomena that occur during the freeze drying process of liposomes, adding a lyoprotectant to the liposome formulation has been extensively reported to inhibit vesicle aggregation, prevent the leakage of the encapsulated material and protect the phospholipid membrane from damage caused by ice crystals [41,42].…”

“…To date, two lyoprotective mechanism-based disaccharides, the water replacement model and the vitrification model, have been proposed in the field of freeze-dried liposomes [41,42,45]. As shown in Figure 3, the former model explained the ability of sugar to replace water by interacting with phospholipids thereby maintaining the space between the phospholipid head groups (loose state) In order to overcome the negative phenomena that occur during the freeze drying process of liposomes, adding a lyoprotectant to the liposome formulation has been extensively reported to inhibit vesicle aggregation, prevent the leakage of the encapsulated material and protect the phospholipid membrane from damage caused by ice crystals [41,42]. A variety of carbohydrates (monosaccharides, disaccharides, polysaccharides and synthetic saccharides), proteins (amino acids) and several alcohols that can interact with phospholipids could act as lyoprotectants (Table 2).…”

“…The latter model describes the formation of a stable sugar glass matrix that can capture dry liposomes during freeze drying [41,45]. In this model, the presence of cryoprotectants between the bilayers, the glass matrix, with a high viscosity but low mobility, is believed to reduce the contact of membranes in proximity thus preventing the aggregation and damage of liposomes caused by ice crystals [41,45]. Currently, Toniazzo et al [46] revealed that the use of sucrose as a lyoprotectant could maintain the average hydrodynamic diameter and zeta potential of lyophilized quercetin-loaded liposomes.…”

“…Freeze drying or lyophilization is a water removal process that involves three major steps: 1. freezing (of a liposome-cryoprotectant mixture); 2. primary drying (where sublimation occurs) and 3. secondary drying (to reduce the residual moisture content) [ 39 ]. This process is one of the most widely used techniques for increasing the long-term stability of liposomes and preventing the degradation of sensitive substances encapsulated in the structure of liposomes [ 12 , 40 , 41 ]. However, the elimination of water through the freeze drying process may cause several adverse effects on the liposome such as changes in the vesicle size, a loss of membrane integrity, a loss of the encapsulated substance and an alteration of the rheological properties.…”