Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules

The aim of our work was to examine the relationship between modifications o f the surface of nanocapsules (NC) by adsorption or covalent grafting of po ly(ethylene oxide) (PEG), and changes in their phospholipid (PL) content on complement activation (C3 cleavage) and on uptake by macrophages. The phys icochemical characterization of the NC included an investigation of their p roperties, such as surface charge, size, hydrophilicity, morphology and hom ogeneity. This is the first time that such properties have been correlated with biological interactions for NC, a novel carrier system with a structur e more complex than nanospheres. C3 crossed immunoelectrophoresis revealed the reduced activation for NC with longer PEG chain and higher density, alt hough all formulations induced C3 cleavage to a lesser or greater extent. N C bearing PEG covalently bound to the surface were weaker activators of com plement than plain PLA [poly(D,L-lactide)] NC or nanospheres (NS). Furtherm ore, 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 lev el of protein binding to NC covered with a high density of 20 kDa PEG chain s is likely to be due to the steric barriers surrounding these particles, w hich prevents protein adsorption and reduces their interaction with macroph ages. (C) 2001 Elsevier Science Ltd. All rights reserved.