Interaction with Phagocytic Cells

The ability of various PEG-coated nanoparticles to avoid the uptake by phagocytic cells extracted from human donor blood (such as monocytes and lymphocytes) or by phagocytic cells in culture (J774 and THP-1) has been extensively studied [43, 62, 64, 66-68].

The uptake of PLA nanospheres both by monocytes and by lymphocytes was reduced when the particles were coated during their preparation process with PEG [62, 66]. After incubation with human monocytes in serum and in plasma, the in vitro cellular uptake of PEG-coated PLA nanospheres was found to be related to the PEG chain length and surface density [67]. Both PEG configurations ("loop" and "brush," see Fig. 2) were found to have equivalent abilities to reduce cellular uptake.

The phagocytosis by human polymorphonuclear cells (PMN) of a series of PEG-PLA nanospheres with various PEG surface densities was studied [64]. Interestingly, the same threshold (distance of about 2 nm between two terminally attached PEG chains) was found to simultaneously minimize plasma protein adsorption, zeta potential, and uptake by PMN cells. The uptake kinetics of PLA and PEG-PLA nanospheres by THP-1 cells was investigated [43]. The PEG-PLA nanospheres were four to eight times less associated to the THP-1 cells than the PLA ones. The necessary distance between two terminally attached PEG 2000 g/mol chains to avoid phagocytosis was found to be in the range of 1.2-1.4 nm.

Similar abilities of the PEG coating to reduce the uptake of phagocytic cells also was found in the case of nano-capsules. The PEG-PLA nanocapsules were about 3- to 13fold less associated to the macrophage-like cell line J774A1 than the PLA ones [68]. The importance to covalently attach PEG to the surface to obtain stable coatings and, therefore, low uptake was emphasized.

0 0

Post a comment