title: Time-dependent changes in opsonin amount associated on nanoparticles alter their hepatic uptake characteristics.
abstract: The relationship between the time-dependent change in serum proteins adsorbed on nanoparticles and their disposition to the liver was investigated by employing lecithin-coated polystyrene nanosphere with a size of 50 nm (LNS-50) as a model nanoparticle in rats. The total amount of proteins adsorbed on LNS-50 increased and the qualitative profile of serum proteins adsorbed on LNS-50 changed during the incubation with serum up to 360 min. The liver perfusion study indicated that the hepatic uptake of LNS-50 incubated with serum for 360 min was significantly larger than those of LNS-50 incubated for shorter period. It was suggested that the increase in the hepatic uptake of LNS-50 with the increase in incubation time would be ascribed mainly to the increase in the opsonin-mediated uptake by Kupffer cells. Semi-quantification of major opsonins, complement C3 (C3) and immunoglobulin G (IgG), and in vitro uptake study in primary cultured Kupffer cells demonstrated that the increase in C3 and IgG amounts adsorbed on LNS-50 was directly reflected in the increased disposition of LNS-50 to Kupffer cells. These results indicate that the amounts of opsonins associated on nanoparticles would change over time and this process would be substantially reflected in the alteration of their hepatic disposition characteristics.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-Naka, Okayama 700-8530, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nagayama
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ogawara
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Fukuoka
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Higaki
authors.forename: Toshikiro
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000327:Adsorption; D000818:Animals; D019540:Area Under Curve; D001798:Blood Proteins / Q000737:chemistry; D015153:Blotting, Western; D002478:Cells, Cultured; D003176:Complement C3 / Q000008:administration & dosage / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005682:Gadolinium / Q000494:pharmacology; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000737:chemistry; D066298:In Vitro Techniques; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D053758:Nanoparticles; D009895:Opsonin Proteins / Q000008:administration & dosage* / Q000032:analysis*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D011137:Polystyrenes; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; D003176:Complement C3; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D010713:Phosphatidylcholines; D011137:Polystyrenes; D005682:Gadolinium; D014357:Trypsin; C038958:gadolinium chloride