title: Effect of poly(N-vinyl-pyrrolidone)-block-poly(D,L-lactide) as coating agent on the opsonization, phagocytosis, and pharmacokinetics of biodegradable nanoparticles.
abstract: The effect of the coating polymer poly(N-vinyl-pyrrolidone) (PVP) on the protein adsorption, phagocytosis, and pharmacokinetics of poly(D,L-lactide)-based nanoparticles was evaluated in vitro and in vivo. Control poly(ethylene glycol) (PEG)-coated nanoparticles were included for comparison. While no difference between PEG- and PVP-decorated nanoparticles in terms of amount of adsorbed protein was evident upon incubation in single protein solutions (BSA, IgG), incubation in serum revealed a protein adsorption pattern both quantitatively and qualitatively distinct. Larger amounts of complement components and immunoglobulins were found to adhere to PVP-coated particles, whereas PEG particles showed preferential adsorption of apolipoproteins. Furthermore, preopsonization in fresh rather than heat-inactivated serum enhanced uptake of both types of particles by murine RAW 264.7 macrophages. However, when isolated rat Kupffer cells were employed, activation of the complement system significantly enhanced the uptake of PVP-coated nanoparticles compared to PEG particles. Ultimately, PVP-coated nanoparticles exhibited considerably shorter circulation times compared to their PEG counterparts when administered intravenously to rats.
authors.affiliation: Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, C.P. 6128, Downtown Station, Montreal, Qc, H3C 3J7, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Gaucher
authors.forename: Kinji
authors.initials: K
authors.lastname: Asahina
authors.forename: Jiaohong
authors.initials: J
authors.lastname: Wang
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Leroux
mesh_terms: D000327:Adsorption; D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003167:Complement Activation / Q000187:drug effects*; D007728:Kupffer Cells / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010587:Phagocytosis / Q000187:drug effects*; D010599:Pharmacokinetics; D011092:Polyethylene Glycols / Q000494:pharmacology; D011137:Polystyrenes / Q000494:pharmacology*; D011145:Polyvinyls / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats
chemical_list: D020099:Coated Materials, Biocompatible; D011137:Polystyrenes; D011145:Polyvinyls; D011506:Proteins; C522357:poly(N-vinyl-pyrrolidone)-block-poly(D,L-lactide); D011092:Polyethylene Glycols