Investigating drug-liposome interactions using liposomal electrokinetic chromatography

Area of Science:

• Analytical Chemistry
• Pharmaceutical Sciences
• Biophysical Chemistry

Background:

• Drug-membrane interactions are critical for drug delivery and efficacy.
• Understanding these interactions requires robust and rapid evaluation methods.
• Liposomes are widely used in drug delivery systems, necessitating characterization of their interactions with active pharmaceutical ingredients (APIs).

Purpose of the Study:

• To establish liposomal electrokinetic chromatography (LEKC) as a method for rapid, simultaneous evaluation of drug-membrane interactions.
• To assess the sensitivity of these interactions to physiological parameters like pH, temperature, and lipid composition.
• To classify drug molecules based on their interaction profiles with liposomes.

Main Methods:

• Utilized liposomal electrokinetic chromatography (LEKC) with nine model drug substances.
• Investigated the effect of varying liposome concentration in the background electrolyte.
• Employed liposomes derived from bovine liver and heart tissue extracts to explore lipid composition effects.
• Examined the influence of temperature and pH on drug-liposome interactions during separation.

Main Results:

• Increased liposome concentration significantly altered API separation kinetics, affecting mobility and peak shapes.
• Liposomes from different tissue sources exhibited distinct interaction profiles based on lipid composition.
• Canagliflozin showed altered migration in the presence of negatively charged liposomes.
• Mobility of positively charged drugs (ambroxol, maraviroc) was suppressed with significant peak tailing.
• Higher temperatures generally enhanced effective mobility due to reduced viscosity and increased lipid bilayer fluidity.
• pH variations (6.0-8.0) introduced complex effects on drug-liposome interactions due to combined API ionization and liposome surface charge changes.

Conclusions:

• Liposomal electrokinetic chromatography is a valuable tool for rapid drug-membrane interaction assessment.
• Liposome composition, temperature, and pH are critical factors influencing drug-liposome interactions.
• Findings are crucial for optimizing liposome-based drug delivery systems and predicting drug behavior in vivo.