Physical conjugation of (tri-) block copolymers to liposomes toward the construction of sterically stabilized vesicle systems

The physical conjugation of (tri-) block copolymer molecules to phospholipid vesicle bilayers in order to construct sterically stabilized vesicles can be carried out in two different ways: by allowing the copolymer molecules to freely participate in the small unilamellar vesicle (SUV) formation process along with the lipids or by adding the copolymer molecules to pre-formed small unilamellar liposomes. Structurally and morphologically different copolymer coated vesicle systems occur. The effect on the mean vesicle diameter and the vesicle surface characteristics is monitored by dynamic light scattering and laser Doppler electrophoresis techniques for a wide variety of block copolymer molecules of the PEO-PPO-PEO type (PEO is poly(ethylene oxide); PPO poly(propylene oxide)). Systematic investigations as a function of copolymer added concentration and molecular structure were undertaken throughout. The results indicate a dramatic increase in mean vesicle diameter when the polymer molecules are present during vesiculation, while in the case of copolymer addition to already formed liposomes the mean vesicle size follows a classic Langmuirian-type adsorption curve as a function of copolymer concentration. The zeta-potential values obtained decrease in a very similar pattern irrespective of the way of addition for the large PF127 (PEO99-PPO65-PEO99) molecule, illustrating the presence of polymer chains at the vesicle surface. For the small, more hydrophobic L61 (PEO10-PPO16-PEO10) molecule, the reduced zeta-potential value is maintained only when the copolymer molecules participate in bilayer formation, indicating absence of interaction between the polymer and the lipids when added to preformed liposomes, due to the preferred copolymer tendency to aggregate into micelles separate from the lipid bilayer particles (that eventually leads to phase separation). According to the molecular models proposed to describe the occurring lipid-copolymer interactions, addition of copolymer molecules after liposomes have been formed leads to their adsorption onto the outer liposome surface, its effectiveness being dependent on the influence that the hydrophilic (PEO) and hydrophobic (PPO) blocks exert on the copolymer molecular behaviour. Copolymer-lipid coparticipation toward bilayer formation, at low added polymer concentrations, leads to PPO block protection by arranging along with the lipids as integral parts of the vesicle bilayer, hence anchoring the PEO chains that dangle in the aqueous solution onto the vesicles. Simple geometrical considerations are also included, reinforcing the theoretical feasibility of the described models. The latter type of physically conjugating polymer chains onto vesicle surfaces is proposed as an improved alternative to the weak adsorption of amphiphilic molecules and the cumbersome chemical modification of the lipid polar headgroups to confer steric protection to liposomal surfaces.