Trehalose and dry dipalmitoylphosphatidylcholine revisited

Area of Science:

• Biophysics
• Materials Science
• Physical Chemistry

Background:

• Liposomes, such as dipalmitoylphosphatidylcholine (DPPC) vesicles, are widely used in drug delivery and biomaterials.
• Preserving the structural integrity of lipid vesicles in a dry state is challenging due to phase transitions.
• Trehalose is a disaccharide known for its potential to stabilize biological molecules and membranes.

Purpose of the Study:

• To investigate the effect of trehalose on the phase transition temperature of DPPC vesicles in dry mixtures.
• To determine the optimal conditions for trehalose-mediated stabilization of DPPC vesicles.

Main Methods:

• Differential scanning calorimetry (DSC) to measure phase transition temperatures.
• Fourier transform infrared spectroscopy (FTIR) to analyze molecular interactions and structural changes.
• Freeze-fracture electron microscopy (FFEM) to visualize vesicle morphology and integrity.

Main Results:

• Dry DPPC/trehalose mixtures with 0.2 mol water/mol lipid exhibited a significantly lowered gel to liquid-crystalline transition temperature (Tm) of 24°C when trehalose was present during drying in the liquid-crystalline phase.
• Pure dry DPPC showed a high Tm of 105-112°C, while hydrated pure DPPC had a Tm of 42°C.
• The presence of trehalose effectively stabilized the DPPC vesicles in a dry state, preventing the high-temperature transitions observed in pure dry DPPC.

Conclusions:

• Trehalose acts as a cryoprotectant and lyoprotectant for DPPC vesicles, significantly lowering their phase transition temperature.
• Drying DPPC vesicles in the presence of trehalose, while the lipid is in its liquid-crystalline phase, is an effective strategy for achieving a stable dry formulation.
• These findings have implications for the storage and formulation of lipid-based delivery systems.