The Role of Cryoprotective Agents in Liposome Stabilization and Preservation

Abstract

To improve liposomes’ usage as drug delivery vehicles, cryoprotectants can be utilized to prevent constituent leakage and liposome instability. Cryoprotective agents (CPAs) or cryoprotectants can protect liposomes from the mechanical stress of ice by vitrifying at a specific temperature, which forms a glassy matrix. The majority of studies on cryoprotectants demonstrate that as the concentration of the cryoprotectant is increased, the liposomal stability improves, resulting in decreased aggregation. The effectiveness of CPAs in maintaining liposome stability in the aqueous state essentially depends on a complex interaction between protectants and bilayer composition. Furthermore, different types of CPAs have distinct effective mechanisms of action; therefore, the combination of several cryoprotectants may be beneficial and novel attributed to the synergistic actions of the CPAs. In this review, we discuss the use of liposomes as drug delivery vehicles, phospholipid–CPA interactions, their thermotropic behavior during freezing, types of CPA and their mechanism for preventing leakage of drugs from liposomes.

Lyophilization process optimization and molecular dynamics simulation of mRNA-LNPs for SARS-CoV-2 vaccine

“…In the present study, we found that the lyophilization procedure and lyoprotectant were related to each other rather than acting independent of each other [33][34][35] . The suitable lyoprotectant increased the eutectic point and collapsed the temperature of the system.…”

Long-Circulating and Fusogenic Liposomes Loaded with Paclitaxel and Doxorubicin: Effect of Excipient, Freezing, and Freeze-Drying on Quality Attributes

“…When liposomes are frozen, the excipient keeps the size of the liposomes constant, while also reducing the osmotic gradient caused by cryo-concentration. On the contrary, the excipient stabilizes the lipid bilayers in the liposomes’ outer compartment, limiting changes in their physical characteristics and eventual drug leakage [ 9 ].…”

“…The freezing separates most of the solvent from liposomes and excipients, resulting in the formation of ice crystals [ 3 , 5 ]. Since water molecules interacting with polar moieties of liposome lipids contribute to spatial membrane distribution, dehydration may favor vesicle fusion/aggregation and modify the packing density and transition temperature of lipids [ 2 , 8 , 9 ].…”

Nanobiotechnology-Enabled mRNA Stabilization

“…Therefore, cryoprotectants such as saccharides are introduced [ 73 ]. The addition of sugar cryoprotectants lowers the concentration of water, therefore inhibiting ice development [ 28 , 74 ]. In addition, sugar cryoprotectants can interact with the NP surface (e.g., phospholipid heads of LNPs) via hydrogen bonds [ 28 , 74 ], displacing the water hydration layer on the NP surface.…”

“…The addition of sugar cryoprotectants lowers the concentration of water, therefore inhibiting ice development [ 28 , 74 ]. In addition, sugar cryoprotectants can interact with the NP surface (e.g., phospholipid heads of LNPs) via hydrogen bonds [ 28 , 74 ], displacing the water hydration layer on the NP surface. Thus, the movement of water molecules during freezing and thawing has minimal effect on the shape and size of the whole mRNA formulation, minimizing mRNA leakage, and thereby enhancing its stability [ 71 ].…”