Evaluation of amphiphilic PEG derivatives as surface modifiers for the production of stealth liposomes

Some amphiphilic conjugates of amino- or carboxy-mPEG(2000) or mPEG(5000) with a series of lipoamino acids as a lipid anchor (PEG-LAA), recently synthetized as novel surface modifiers for drug nanocarriers, were used to decorate the surface of multilamellar liposomes (MLV). For comparison, MLV were also prepared using commercial PEG lipid derivatives (DSPE-PEG and PEG 40 monostearate), commonly used to produce stealth nanocarriers. Two experimental models were used to check the ability of the PEG-LAA conjugates to organize themselves on the surface of liposomes: an in vitro uptake study, using murine macrophage cultures, that confirmed the ability of PEG-LAA conjugates to hinder or retard the cellular internalization of the vesicles. Second, the measurement of the zeta potential values of negatively charged MLV produced with the various PEG-LAAs, which confirmed their shielding effect on the MLV surface charge, linearly to their molar concentration and as a function of the structures of PEG and LAA used.