Phase behaviour of amphotericin B multilamellar vesicles.

Area of Science:

• Lipid Bilayer Biophysics
• Drug Delivery Systems
• Physical Chemistry

Background:

• Liposomal amphotericin B's efficacy and side effects are linked to its physical properties.
• Understanding the molecular nature of hydrated liposomal preparations is crucial.

Purpose of the Study:

• To investigate the phase behavior of amphotericin B in multilamellar liposomes using differential scanning calorimetry (DSC).
• To characterize the molecular interactions between amphotericin B and phospholipid matrices.

Main Methods:

• Differential scanning calorimetry (DSC) was used to analyze the phase transitions of liposomes.
• Liposomes were composed of dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) with varying drug concentrations.
• Comparative analyses were performed using different phospholipid compositions, including unsaturated phosphatidylcholines.

Main Results:

• DSC revealed that amphotericin B tends to form a rigid phase within the liposome membrane.
• Fluidization onset temperatures were minimally affected by the drug, especially in unsaturated phospholipid matrices.
• Drug-induced alterations in melting profiles were less pronounced than in previously studied sonicated preparations.

Conclusions:

• Amphotericin B likely exists as oligomers within the phospholipid matrix, contributing to its phase separation.
• The liposomal preparation studied demonstrated thermodynamic stability.
• Findings provide insights into the physical chemistry of liposomal amphotericin B, relevant for therapeutic applications.