Stability Risks After Formation

Once liposomes are formed, preserving their physical properties can be challenging. Size distributions can drift as components degrade, and partial membrane permeabilization can allow encapsulated cargo to leak. Hydrolytic degradation is a common issue for lipid-based systems.

pH & Temperature—Store Neutral and Cold

Aqueous drug formulations are generally less stable because bulk water accelerates hydrolysis of lipids. After sizing, store suspensions as close to pH ~7 as possible. Lipids with ester-linked acyl chains are vulnerable to both acid- and base-catalyzed hydrolysis. Because hydrolysis rates rise sharply with temperature, keep liposome suspensions refrigerated during storage.

No Freezing; Use Protectants & Antioxidants

Avoid freezing: ice formation can fracture vesicles, shift the size distribution, and promote cargo loss. When cold-chain interruption or lyophilization cannot be avoided, cryoprotectants such as dextrose, sucrose, or trehalose can improve stability against hydrolysis and freezing stress. Samples may also undergo oxidation during storage; adding small amounts of antioxidants during processing can help stabilize the suspension and limit lipid oxidation.

Handling SUVs vs LUVs; Expected Shelf Behavior

SUVs (small unilamellar vesicles) should not be held above their phase transition temperature (Tm) for more than ~24 hours. LUVs (large unilamellar vesicles) may be stored for longer when kept at 4–8 °C while not in use. Hydrolysis begins immediately upon storage and generates mono-acyl derivatives (lysolipids) that behave as detergents and disrupt bilayer integrity, thereby increasing permeability. After ~5–7 days at 4–8 °C, leakage of internal contents typically becomes detectable, indicating hydrolytic degradation. If precise membrane structure is not critical for your application, liposomes can often be stored for 1–2 months with <10% hydrolytic degradation.

Aladdin: https://www.aladdinsci.com/