Colloids and Surfaces B: Biointerfaces 18 (2000) 301 – 313 ‘Stealth’ corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption R. Gref a *, M. Lu ¨ck b , P. Quellec c , M. Marchand d , E. Dellacherie c , S. Harnisch b , T. Blunk e , R.H. Mu ¨ ller b a Physico -Chimie, Pharmacotechnie, Biopharmacie, UMR CNRS 8612, Uniersite ´ Paris Sud, Centre d’Etudes Pharmaceutiques, 5, Rue J.B. Cle ´ment, Cha ˆtenay Malabry, France b Department of Pharmaceutics, Biopharmaceutics and Biotechnology, The Free Uniersity of Berlin, Berlin, Germany c Laboratoire de Chimie -Physique Macromole ´culaire UMR 7568, ENSIC, Nancy, France d Etablissement de Transfusion Sanguine, Nancy, France e Massachusetts Institute of Technology, Cambridge, MA, USA Abstract Nanoparticles possessing poly(ethylene glycol) (PEG) chains on their surface have been described as blood persistent drug delivery system with potential applications for intravenous drug administration. Considering the importance of protein interactions with injected colloidal dug carriers with regard to their in vivo fate, we analysed plasma protein adsorption onto biodegradable PEG-coated poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(-caprolactone) (PCL) nanoparticles employing two-dimensional gel electrophoresis (2-D PAGE). A series of corona/core nanoparticles of sizes 160 – 270 nm were prepared from diblock PEG-PLA, PEG-PLGA and PEG-PCL and from PEG-PLA:PLA blends. The PEG Mw was varied from 2000–20 000 g/mole and the particles were prepared using different PEG contents. It was thus possible to study the influence of the PEG corona thickness and density, as well as the influence of the nature of the core (PLA, PLGA or PCL), on the competitive plasma protein adsorption, zeta potential and particle uptake by polymorphonuclear (PMN) cells. 2-D PAGE studies showed that plasma protein adsorption on PEG-coated PLA nanospheres strongly depends on the PEG molecular weight (Mw) (i.e. PEG chain length at the particle surface) as well as on the PEG content in the particles (i.e. PEG chain density at the surface of the particles). Whatever the thickness or the density of the corona, the qualitative composition of the plasma protein adsorption patterns was very similar, showing that adsorption was governed by interaction with a PLA surface protected more or less by PEG chains. The main spots on the gels were albumin, fibrinogen, IgG, Ig light chains, and the apolipoproteins apoA-I and apoE. For particles made of PEG-PLA45K with www.elsevier.nl/locate/colsurfb * Tel.: +33-1-46835581; fax: +33-1-46619334. E-mail address: ruxandra.gref@cep.u-psud.fr (R. Gref). 0927-7765/00/$ - see front matter © 2000 Elsevier Science B.V. All rights reserved. PII:S0927-7765(99)00156-3