pH-sensitive, plasma-stable liposomes with relatively prolonged residence in circulation.

Area of Science:

• Lipid nanoparticle formulation
• Drug delivery systems
• Biomaterials science

Background:

• Acid-sensitive liposomes are effective for cytoplasmic delivery.
• Liposomes of DOPE and DPSG maintain acid-sensitivity post-plasma exposure.

Purpose of the Study:

• To investigate the impact of ganglioside GM1 on liposome blood circulation time.
• To evaluate the stability and biodistribution of GM1-containing liposomes.

Main Methods:

• Liposomes composed of DOPE and DPSG (4:1 molar ratio) with varying GM1 content were prepared.
• Acid-sensitivity was assessed by measuring content release at pH 4.
• Plasma stability was evaluated after incubation with human plasma.
• Biodistribution studies were conducted in Balb/c mice using 125I-labeled tyraminylinulin.

Main Results:

• Increasing GM1 content reduced acid-sensitivity, but partial sensitivity remained up to 5% GM1.
• GM1 inclusion minimally affected release in human plasma.
• GM1-containing liposomes exhibited increased blood levels and reduced liver/spleen uptake.
• Liposomes demonstrated pH-sensitivity, plasma-stability, and prolonged circulation.

Conclusions:

• GM1 incorporation in DOPE/DPSG liposomes enhances circulation time.
• These liposomes maintain pH-sensitivity and plasma-stability.
• GM1-containing liposomes are promising candidates for in vivo drug delivery.