Exploring the Impact of Liposome Surface Charge on Drug Delivery Systems

DOTAP-containing liposomes show that liposome surface charge modulates protein corona formation and, consequently, drug-delivery behavior. The team measured zeta potential shifts and protein adsorption (including albumin) to quantify surface–protein interactions. Clinically, these data tie formulation charge choices to biodistribution and clearance risks in preclinical models.

The study compared liposomal formulations with graded cationic lipid content and measured their interactions with serum proteins in vitro. Zeta potential and protein‑binding assays captured both electrostatic state and adsorbed mass, so these endpoints predict relative in vivo interaction potential by indicating likely changes in corona composition and surface identity.

Increasing DOTAP shifted zeta potential from negative toward strongly positive and increased protein adsorption—demonstrating a charge‑dependent adsorption pattern. Higher DOTAP raises surface positive charge density, strengthening electrostatic attraction to negatively charged serum proteins and increasing both corona composition and density.

Magnesium chloride reduced protein adsorption by screening electrostatic forces and partially competing at binding sites on proteins and lipid headgroups. Ionic shielding diminishes the effective coulombic attraction between cationic surfaces and anionic serum proteins, thereby lowering corona formation. Thus, ionic conditions during formulation or administration can materially change corona outcomes and modulate potential immune interactions.

Looking ahead, targeted preclinical biodistribution and immunogenicity testing that systematically varies surface charge and ionic conditions will better define clinical translation risk and opportunity.