Binding and uptake of liposomes containing a poly(ethylene glycol) derivative of cholesterol (stealth liposomes) by the macrophage cell line J774: influence of PEG content and its molecular weight.

The binding and intake of liposomes containing a different molar content and chain length of a PEG-Chol derivative had been studied in cultured macrophage cell line J774. The decrease in binding and endocytosis of the liposomes containing PEG-Chol is dependent on (i) the PEG chain length, (ii) the molar content of the surfactant, (iii) the liposome concentration in the external medium. The best results in reducing the uptake of liposomes were obtained by a PEG-Chol liposome suspension with a high molar content (25%) which presents a non negligible amount of free PEG-Chol. Moreover, we could show an increase by 2 for binding and by about 5 for endocytosis of filtrated-liposomes containing 25 mol% of 8800PEG-Chol, in the absence of free PEG-Chol in the suspension. Binding and intake of control liposomes was also inhibited in the presence of free PEG-Chol. Fluid phase endocytosis of SRh was inhibited up to 45% of control in the presence of liposomes containing PEG-Chol or free PEG-Chol. Based on the comparison of 4400PEG-Chol with the most commonly used PEG derivative 5000PEG-PE, PEG-Chol is more powerful in terms of reducing their binding and endocytosis by J774 cells. Inhibition of the fluid phase endocytic process is attributed to the binding of PEG-Chol to the cells' plasma membrane inducing a decrease in surface hydrophobicity of the cells, resulting in a marked decrease in the extent of phagocytic ingestion.