Aggregation of PEGylated liposomes driven by hydrophobic forces

Abstract

2 Graphical Abstract 3 Highlights Kosmotropes induce the aggregation and fusion of PEG-liposomes.  The effect depends on both the kosmotrope and PEG concentration.  Aggregation is reversible under certain conditions.  Kosmotropes lead to a dehydration-related conformational change of the PEG polymer.  The likely driving force behind aggregation is the hydrophobic effect. 4 ABSTRACTPolyethylene glycol (PEG) is widely used to sterically stabilize liposomes and improve the pharmacokinetic profile of drugs, peptides and nanoparticles. Here we report that ammonium sulfate (AS) can evoke the aggregation of PEGylated vesicles in a concentration-dependent manner. Liposomes with 5 mol% PEG were colloidally stable at AS concentrations up to 0.7 mM, above which they precipitated and formed micron-size aggregates with irregular shape. While aggregation was reversible up to 0.9 M of AS, above 1 M fusion occurred, which irreversibly distorted the size distribution. Zeta potential of liposomes markedly increased from -71±2.5 mV to 2±0.5 mV upon raising the AS concentration from 0 to 0.1 M, but no considerable increase was seen during further AS addition, showing that the aggregation is independent of surface charge. There was no aggregation in the absence of the PEG chains, and increasing PEG molar % shifted the aggregation threshold to lower AS concentrations. Changes in the FTIR spectral features of PEGylated vesicles suggest that AS dehydrates PEG chains. Other kosmotropic salts also led to aggregation, while chaotropic salts did not, which indicates a general kosmotropic phenomenon. The driving force behind aggregation is likely to be the hydrophobic effect due to salting out the polymer similarly to what happens during protein purification or Hydrophobic Interaction Chromatography. Since liposome aggregation and fusion may result in difficulties during formulation and adverse reaction upon application, the phenomena detailed in this paper may have both technological and therapeutical consequences.

Nanovesicles as Vanillin Carriers for Antimicrobial Applications

“…The surface charge is key for the vesicle to interact with the molecule to be encapsulated and with the cell membrane. Typically, low zeta potential is obtained when non-ionic or neutral surfactants are used [ 35 ].…”

Two-Dimensional Empty Liquid Composed of a Patchy Metal Nanoparticle Network Structure for Transparent Plasmonic Devices

“…After evaporation of the solvent, the surfaces were compressed using a Teflon bar to measure the surface pressure (Π) and area per particle (A) curves at room temperature. The AuOA measurements were performed on Milli-Q water, while the AuPEG measurements were performed on 2 mM (NH 4 ) 2 SO 4 and hydrochloric acid (HCl) aqueous solutions. , Kosmotropic salts such as ammonium sulfate are known to promote dehydration of PEG chains and enhance hydrophobic interactions between PEG chains . Additionally, an acidic environment could promote hydrogen bond formation .…”

“…26,27 Kosmotropic salts such as ammonium sulfate are known to promote dehydration of PEG chains and enhance hydrophobic interactions between PEG chains. 26 Additionally, an acidic environment could promote hydrogen bond formation. 27 Although the mechanisms are different, both environments are considered to strengthen the interactions among AuPEG NPs.…”

Span 60/Cholesterol Niosomal Formulation as a Suitable Vehicle for Gallic Acid Delivery with Potent In Vitro Antibacterial, Antimelanoma, and Anti-Tyrosinase Activity

“…If the zeta potential is near zero, the particles will aggregate because they have a low electrostatic repulsion. Generally, when the zeta potential is greater than 35 mV or lower than −35 mV, the particles are considered stable [37].…”