Sugar-based Cryoprotectants Stabilize Liposomal Vesicles by Exhibiting a Cholesterol-like Effect

Area of Science:

• Lipid Nanoparticle Formulation
• Biophysical Chemistry
• Pharmaceutical Sciences

Background:

• Liposomes are prone to aggregation during lyophilization, a critical step for their storage and stability.
• Cryoprotectants are essential additives to prevent structural damage and fusion of liposomes during freeze-drying.
• Understanding cryoprotectant-lipid interactions is key to developing stable liposomal formulations.

Purpose of the Study:

• To compare the efficacy of mannitol (MTL), trehalose (THL), and beta-cyclodextrin (β-CD) as cryoprotectants for soy lecithin (SL) liposomes.
• To investigate the influence of cholesterol (CHL) on the structural characteristics and cryoprotective effects.
• To elucidate the interaction mechanisms between cryoprotectants and liposomes using various analytical techniques.

Main Methods:

• Liposomes were formulated using the ethanol injection method.
• Cryoprotectants (MTL, THL, β-CD) were tested at different concentrations (2, 6, 10 mM).
• Characterization involved scattering, thermal analysis (DSC), and spectroscopic methods (FTIR).

Main Results:

• Cholesterol (CHL) increased liposome hydrodynamic diameter but enhanced vesicle stability through hydrophobic interactions.
• Hydrogen bonding between cryoprotectants and liposomes was confirmed via FTIR, increasing the phase transition temperature (Tm).
• Beta-cyclodextrin (β-CD) demonstrated the highest affinity and cryoprotective effect, showing concentration-dependent interactions.

Conclusions:

• Beta-cyclodextrin (β-CD) is a highly effective cryoprotectant for soy lecithin (SL) liposomes, superior to mannitol (MTL) and trehalose (THL).
• Cryoprotectant choice significantly impacts liposome stability during lyophilization, with β-CD offering optimal protection.
• The study provides valuable insights into cryoprotectant selection for stable liposomal drug delivery systems.