PEGylation of microspheres generates a heterogeneous population of particles with differential surface characteristics and biological performance

Gbadamosi, J.K., Hunter, A.C. and Moghimi, S.M. (2002) PEGylation of microspheres generates a heterogeneous population of particles with differential surface characteristics and biological performance FEBS Letters, 532 (3). pp. 338-344. ISSN 0014-5793

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Abstract

Surface PEGylation of polystyrene microspheres with methoxy-poly(ethylene glycol)-5000 (mPEG-5000) generated a heterogeneous population of entities that differed in surface characteristics and in vitro biological performance (phagocytosis and complement activation). Surface heterogeneity was determined by hydrophobic interaction chromatography, measurements of particle electrophoretic mobility in a defined field and adlayer thickness of the projected mPEG chains. The particle population separation by hydrophobic interaction chromatography demonstrated a remarkable linear relationship between the particle zeta potential and phagocytosis by J774 A1 macrophage-like cells. Microsphere populations bearing a predominant surface of mPEG molecules as high-density mushroom–brush intermediate and/or brush configuration were most resistant to phagocytosis and activated the human complement system poorly. Conversely, those populations with predominant surface mPEGs in a mushroom regime were potent activators of the complement system and were prone to phagocytosis. Therefore, surface heterogeneity explains why a fraction of intravenously injected ‘long-circulating’ nanoparticles is cleared rapidly by macrophages of the reticuloendothelial system. Hydrophobic interaction chromatography can readily assess the extent of surface heterogeneity of PEGylated particulate drug delivery systems and pre-select particles with optimal retention times in the blood. These observations may also be relevant with respect to successful surface camouflaging of cells, drug depots and implantable devices.

Item Type: Journal article
Uncontrolled Keywords: Complement activation; Surface camouflaging; Long-circulating particle; Macrophage; Microsphere; Poly(ethylene glycol)
Subjects: B000 Health Professions > B200 Pharmacology Toxicology and Pharmacy > B210 Pharmacology and Therapeutics
DOI (a stable link to the resource): 10.1016/S0014-5793(02)03710-9
Faculties: Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences > Biomedical Materials
Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences > Chemical Biology
Depositing User: editor spbs
Date Deposited: 08 Nov 2007
Last Modified: 06 Feb 2014 15:43
URI: http://eprints.brighton.ac.uk/id/eprint/647

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