Important role of serum proteins associated on the surface of particles in their hepatic disposition.
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.
Furumoto
Kentaro
K
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
Ogawara
Ken-ichi
K
Nagayama
Susumu
S
Takakura
Yoshinobu
Y
Hashida
Mitsuru
M
Higaki
Kazutaka
K
Kimura
Toshikiro
T
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
D001798:Blood Proteins; D004337:Drug Carriers; D010713:Phosphatidylcholines; D011137:Polystyrenes