Relationships between liposome properties, cell membrane binding, intracellular processing, and intracellular...

Area of Science:

• Biotechnology
• Nanomedicine
• Cell Biology

Background:

• Cationic liposomes show enhanced cellular uptake due to positive surface charge.
• Pegylation, crucial for in vivo applications, reduces liposome internalization.
• Balancing these opposing effects is key for effective liposomal drug delivery.

Purpose of the Study:

• To quantitatively determine the relationships between liposome surface charge, pegylation, cell membrane binding, and intracellular bioavailability.
• To investigate the interplay between stealth properties and cellular internalization.
• To identify optimal parameters for enhanced liposome delivery.

Main Methods:

• Utilized pancreatic Hs-766T cancer cells for experiments.
• Quantified liposome binding (B(eq)) and intracellular residence (I(eq)) at equilibrium.
• Analyzed relationships using regression equations based on zeta potential (ZP) and %PEG.

Main Results:

• Nonlinear and interdependent relationships were observed between surface charge, pegylation, and cellular uptake.
• Intracellular bioavailability showed a positive triphasic relationship with surface charge and a negative biphasic relationship with pegylation.
• A 1% increase in pegylation could be counteracted by a 4 mV increase in zeta potential.

Conclusions:

• Surface charge and pegylation exhibit complex interactions influencing liposome bioavailability.
• It is possible to balance pegylation and surface charge to simultaneously maximize stealth and intracellular delivery.
• Findings provide a quantitative basis for designing improved cationic liposomes for therapeutic applications.