Novel pH-sensitive paramagnetic liposomes with improved MR properties

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Magnetic Resonance Imaging

Background:

• Paramagnetic pH-sensitive liposomes are a novel approach for MRI-based monitoring of pathological pH variations.
• Essential liposome characteristics include blood stability and selective release of encapsulated agents at lower tissue pH.

Purpose of the Study:

• To formulate and characterize novel liposomal systems for pH monitoring using MRI.
• To enhance the stability of existing pH-sensitive liposomes in blood while maintaining pH responsiveness.

Main Methods:

• Liposomal systems were formulated using dipalmitoylphosphatidylethanolamine (DPPE) with different amphiphiles (palmitic acid (PA), dipalmitoylglycerosuccinate (DPSG)).
• Characterization involved relaxometry, cryo-transmission electron microscopy (cryo-TEM), and MRI.
• Stability was assessed in blood, and pH sensitivity was evaluated in buffer and in vitro MRI phantom studies.

Main Results:

• Cholesterol incorporation into DPPE/PA liposomes improved blood stability but reduced pH sensitivity.
• Polyethylene glycol (PEG)-modified DPPE/PA liposomes were pH-insensitive and unstable in blood.
• DPPE/DPSG liposomal GdDTPA-BMA exhibited stability in blood at physiological pH and marked pH sensitivity, with retained sensitivity after blood preincubation.

Conclusions:

• DPPE/DPSG liposomal GdDTPA-BMA represents an improved system for pH-sensitive MRI contrast agents.
• This formulation demonstrates superior stability and pH responsiveness compared to previous systems.
• The study validates the potential of DPPE/DPSG liposomes for in vitro pH monitoring applications via MRI.