The aim of our work was to examine the relationship between modifications
of the surface of nanocapsules (NC) by adsorption or covalent grafting of
poly(ethylene oxide) (PEG), and changes in their phospholipid (PL) content
on complement activation (C3 cleavage) and on uptake by macrophages. The
physicochemical characterization of the NC included an investigation of
their properties, such as surface charge, size, hydrophilicity, morphology
and homogeneity. This is the first time that such properties have been
correlated with biological interactions for NC, a novel carrier system with
a structure more complex than nanospheres. C3 crossed immunoelectrophoresis
revealed the reduced activation for NC with longer PEG chain and higher
density, although all formulations induced C3 cleavage to a lesser or
greater extent. NC bearing PEG covalently bound to the surface were weaker
activators of complement than plain PLA [poly(d,l-lactide)] NC or
nanospheres (NS). Furthermore, the fluorescent/confocal microscopy of
J774A1 cells in contact with NC reveal a dramatically reduced interaction
with PEG-bearing NC. However, the way in which PEG was attached (covalent
or adsorbed) seemed to affect the mechanism of uptake. Taken together,
these results suggest that the low level of protein binding to NC covered
with a high density of 20kDa PEG chains is likely to be due to the steric
barriers surrounding these particles, which prevents protein adsorption and
reduces their interaction with macrophages.