pH-sensitive liposomes: acid-induced liposome fusion

Area of Science:

• Biochemistry
• Materials Science
• Biophysics

Background:

• Liposomes are versatile drug delivery vehicles.
• Understanding liposome fusion is crucial for controlled release applications.
• pH-sensitive liposomes offer targeted delivery strategies.

Purpose of the Study:

• To investigate the pH-dependent fusion of unilamellar liposomes.
• To identify key lipid components influencing liposome fusion kinetics and stability.
• To evaluate the effect of cholesterol on fusion-induced content leakage.

Main Methods:

• Sonication to form unilamellar liposomes.
• Resonance energy transfer (RET) for lipid mixing analysis.
• Gel filtration and electron microscopy for fusion verification.
• Calcein release assay to quantify encapsulation efficiency.

Main Results:

• Liposomes containing phosphatidylethanolamine and palmitoylhomocysteine (PtdEtn/PHC) fused rapidly at pH 5.
• PHC (≥20 mol%) was essential for pH-sensitive fusion.
• PtdEtn enhanced fusion, while phosphatidylcholine inhibited it.
• Cholesterol (40 mol%) reduced content leakage during fusion without hindering the process.

Conclusions:

• PtdEtn and PHC are key components for pH-triggered liposome fusion.
• Cholesterol incorporation can stabilize liposomes against leakage during fusion.
• These findings have implications for developing advanced drug delivery systems.