title: Important role of serum proteins associated on the surface of particles in their hepatic disposition.
abstract: To elucidate the important factors for the difference in the hepatic disposition between polystyrene nanospheres with a size of 50 nm (NS-50) and lecithin-coated NS-50 (LNS-50), the liver perfusion studies and the in vitro uptake studies using the cultured Kupffer cells were performed. It was suggested that opsonin-mediated phagocytosis is not significantly involved in the hepatic disposition of LNS-50 in the presence of serum, whereas its involvement in the hepatic uptake of NS-50 was clearly demonstrated. Western blot analysis showed that IgG, complement C3, and fibronectin, well-known opsonins in the serum, adsorbed on the surface of NS-50 in larger amount than on the surface of LNS-50. On the other hand, serum albumin, which was suggested to function as a dysopsonin for the hepatic disposition of NS-50, was associated with both spheres almost to the same extent. These findings suggest that the hepatic disposition of LNS-50 at lower level should be ascribed to the less amount of serum opsonins associated on the surface and that the serum proteins associated with these spheres should be important as a determinant for their hepatic disposition.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Furumoto
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ogawara
authors.forename: Susumu
authors.initials: S
authors.lastname: Nagayama
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takakura
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Higaki
authors.forename: Toshikiro
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D036103:Nanotechnology / Q000379:methods; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000493:pharmacokinetics; D011137:Polystyrenes / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
chemical_list: D001798:Blood Proteins; D004337:Drug Carriers; D010713:Phosphatidylcholines; D011137:Polystyrenes