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

Paper ID Volume ID Publish Year Pages File Format Full-Text
13565 881 2001 13 PDF Available
Title
Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules
Abstract

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 20 kDa PEG chains is likely to be due to the steric barriers surrounding these particles, which prevents protein adsorption and reduces their interaction with macrophages.

Keywords
Nanocapsules; Poly(d,l-lactide-co-ethylene oxide) copolymers; Complement activation; Cellular uptake; Physicochemical characterization; Surface properties
First Page Preview
Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 22, Issue 22, 15 November 2001, Pages 2967–2979
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering