Stability and aggregation studies of non-sonicated arsonolipid-containing vesicles

Area of Science:

• Lipid Nanoparticle Formulation
• Biophysical Chemistry
• Materials Science

Background:

• Arsonolipid-containing liposomes (arsonosomes) are novel lipid vesicles.
• Understanding their stability is crucial for potential applications.
• Lipid composition is a key factor influencing liposome behavior.

Purpose of the Study:

• To investigate the impact of lipid composition on the stability of non-sonicated arsonosomes.
• To assess membrane integrity and physical stability (size, aggregation) of arsonosomes.
• To evaluate the role of cholesterol (Chol) and distearoyl-phospatidylcholine (DSPC) in arsonosome stability.

Main Methods:

• Preparation of arsonosomes with varying lipid compositions (plain arsonolipids, arsonolipids with Chol, arsonolipids with DSPC).
• Membrane integrity assessment using 5-(6)carboxyfluorescein (CF) leakage assay.
• Physical stability evaluation via photon correlation spectroscopy to monitor size and aggregation, with and without Ca(2+) ions.

Main Results:

• Plain C18 arsonosomes exhibited poor stability, retaining only 15% of incorporated CF after 24 hours.
• Incorporation of cholesterol (1:1 mol/mol) significantly enhanced arsonosome stability.
• Distearoyl-phospatidylcholine (1:1 mol/mol) improved stability to a lesser extent than cholesterol.
• Plain arsonosomes showed rapid aggregation; calcium-induced aggregation was significant but slower.
• Aggregation behavior was not always predictable by zeta potential changes, indicating complexity.

Conclusions:

• Cholesterol is a highly effective excipient for stabilizing arsonolipid liposomes.
• DSPC provides moderate stabilization for arsonosomes.
• Arsonosome aggregation is influenced by lipid composition and the presence of divalent cations like calcium.
• The aggregation process is complex and not solely governed by surface charge.