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Review
. 2022 Oct 18;23(20):12487.
doi: 10.3390/ijms232012487.

The Role of Cryoprotective Agents in Liposome Stabilization and Preservation

George Frimpong Boafo  1 , Kosheli Thapa Magar  2 , Marlene Davis Ekpo  1 , Wang Qian  1 , Songwen Tan  1 , Chuanpin Chen  1
Affiliations
Review

The Role of Cryoprotective Agents in Liposome Stabilization and Preservation

George Frimpong Boafo et al. Int J Mol Sci. .

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.

Keywords: cryoprotectants; drug delivery; freeze drying; freeze-thaw; liposome(s); phospholipid–CPA interactions.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Freezing/lyophilization of drug-loaded liposomes with and without the addition of cryoprotective agents (CPAs).
Figure 2
Figure 2
Classification of liposomes based on their composition. (A) Conventional liposome, (B) pH sensitive liposome, (C) long circulating liposome, (D) temperature-sensitive, enzyme-sensitive, light-sensitive, and magnetic-response liposomes.
Figure 3
Figure 3
Classification of liposomes based on their lipid bilayer structure and size. (A) Small Unilammelar Vesicles (SUV), (B) Large Unilammelar Vesicles (LUV), (C) Giant Unilammelar Vesicles (GULV), (D) Multivesicular Liposome, (E) Multilammelar Liposome.
Figure 4
Figure 4
An illustration of the interactions between liposomes and cells.
Figure 5
Figure 5
An illustration of the thermotropic behavior of hydrated phospholipids in both phase transition temperature (Tm) and pre-transition temperature (Tp).
Figure 6
Figure 6
The effect of sugar to phospholipid bilayers before and after dehydration.
See this image and copyright information in PMC

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