Complexation of phosphocholine liposomes with polylysine. Stabilization by surface coverage versus aggregation

Complexation between linear poly-l-lysine (PLL) and negatively charged phosphocholine unilamellar liposomes has been investigated by means of dynamic light scattering, microelectrophoresis, and differential scanning calorimetry. It is found that complexation results in charge inversion (vesicle coating/stabilization) or vesicle aggregation depending on various experimental conditions. Complexation in dependence on PLL concentration and molecular mass, lipid phase state, rate and order of liposome and PLL mixing and time evolution of complexes are investigated and discussed. Aggregation profiles are determined and size distribution of the aggregates formed is studied, leading to the possibility of aggregation control. The time evolution of vesicle aggregation shows particle enlargement consisting in particle growth up to the irreversible formation of thermodynamically stable aggregates of about 2 μm in diameter. The formation of stable aggregates is in agreement with theoretical predictions of colloid particles aggregation by an interplay of long range electrostatic repulsion and short range attraction. Differential scanning calorimetry reveals that physical adsorption occurs exclusively on the vesicle surface and the lipidic organization is not significantly disturbed. The present study describes multivariable aspects of the complexation process between liposomes and polyions which results in the formation of a new class of still poorly defined colloids. These results allow establishing and optimization of a procedure for fabrication of polycation-stabilized vesicles to be used for various applications such as drug delivery.