Highly Stable Liposomes Based on Tetraether Lipids as a Promising and Versatile Drug Delivery System

Area of Science:

• Biochemistry
• Materials Science
• Pharmaceutical Sciences

Background:

• Conventional liposomes exhibit limited stability, restricting their use beyond intravenous administration.
• Liposomes offer advantages in drug encapsulation and physicochemical properties for oral and pulmonary drug delivery.

Purpose of the Study:

• To investigate the feasibility and stability of liposomes incorporating tetraether lipids (TEL) from *Thermoplasma acidophilum*.
• To evaluate the impact of varying TEL:Phospholipon 100H (Ph) molar ratios on liposome stability.

Main Methods:

• Liposomes with different TEL:Ph ratios were fabricated and subjected to various temperature and pH conditions.
• Dynamic and electrophoretic light scattering were used to assess size, polydispersity index, and zeta potential.
• Stability was tested post-autoclaving, and 5(6)-carboxyfluorescein leakage was measured in the presence of fetal calf serum (FCS) and lung surfactant (Alveofact).

Main Results:

• TEL incorporation significantly improved liposome stability against low pH, elevated temperatures, and autoclaving sterilization.
• Atomic force microscopy confirmed stable liposome size and morphology after incubation with FCS.
• Increasing the TEL:Ph molar ratio enhanced structural stability against various stress factors.

Conclusions:

• Liposomes formulated with tetraether lipids demonstrate superior stability for potential oral and pulmonary drug delivery applications.
• The enhanced stability profile of TEL-containing liposomes supports their use in challenging environments and sterilization processes.