title: Mechanisms of hepatic disposition of polystyrene microspheres in rats: effects of serum depend on the sizes of microspheres.
abstract: To study the mechanisms of the hepatic disposition of polystyrene microspheres (MS), effects of serum on their hepatic disposition characteristics were investigated for MSs with particle sizes of 50 nm (MS-50) and 500 nm (MS-500) by isolated liver perfusion experiments. It was revealed that serum in the perfusate inhibited and promoted the hepatic disposition of MS-50 and MS-500 at 37 degrees C, respectively. However, pre-heating at 56 degrees C or pre-treatment with anti-C3 antibody of serum reduced the promotive effect of serum on the hepatic uptake of MS-500, suggesting that the complement system should be involved as opsonins for the hepatic uptake of MS-500. Hepatic disposition of both MSs at 4 degrees C was reduced by the addition of serum into the perfusate, which could be ascribed to the reduction of the surface hydrophobicity of MSs due to the adsorption of serum proteins onto the surface of MSs and to resultant decrease in non-specific disposition to the liver. From these results, serum was found to function both as the opsonin to enhance the hepatic uptake of MSs and as the inhibitor by reducing non-specific interaction between MSs and the plasma membrane. Whether serum promotes or inhibits the hepatic disposition of MSs would be dependent on the particle sizes of MSs.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ogawara
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: J
authors.initials: J
authors.lastname: Kubo
authors.forename: M
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Takakura
authors.forename: M
authors.initials: M
authors.lastname: Hashida
authors.forename: K
authors.initials: K
authors.lastname: Higaki
authors.forename: T
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000502:physiology*; D003080:Cold Temperature; D003176:Complement C3 / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D010316:Particle Size; D010477:Perfusion; D010587:Phagocytosis; D011137:Polystyrenes / Q000097:blood* / Q000493:pharmacokinetics*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001798:Blood Proteins; D003176:Complement C3; D011137:Polystyrenes