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Polyethylene glycol (PEG) modification of liposomes is one of the most commonly applied ways of increasing both in vitro and in vivo stability of liposomes. The formed liposomes are commonly referred to as stealth liposomes because the PEG corona renders the liposomes invisible to the macrophages in the bloodstream. The first detailed small-angle neutron scattering analysis of PEG-modified liposomes is presented here. An analytical model for the PEG-modified liposomes is derived, where the liposomes are described as a water core surrounded by a bilayer lipid film with grafted polymer chains in a Gaussian random coil conformation attached to the inside and the outside lipid leaflets. There is an excellent agreement between the obtained experimental data and the proposed structural model of the liposomes. These results are the most direct proof of the structure of the PEG-modified liposomes presented so far, and the described formalism may easily be generalized to more complex liposome structures such as synaptic vesicles.

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