Hepatic uptake of negatively charged particles in rats: possible involvement of serum proteins in recognition by scavenger receptor.
The mechanisms involved in the hepatic uptake of negatively charged carboxylated-polystyrene nanospheres with a size of 50 nm (CNS-50) were examined in rats. The liver perfusion experiments revealed that hepatic disposition of CNS-50 in the absence of serum could be partially ascribed to the direct recognition of the surface negative charge by scavenger receptors. On the other hand, the apparent negative charge of CNS-50 surface dramatically reduced in the presence of serum, because the adsorption of serum protein on their surface results in masking their intrinsic negative charge. However, hepatic disposition of CNS-50 in the presence of serum was significantly inhibited by poly inosinic acid (poly I), a typical inhibitor for scavenger receptors, and the extent of inhibition by poly I was even larger than that in the absence of serum, suggesting that the serum proteins associated on CNS-50 surface could be recognized by scavenger receptors. These results indicate that not only the intrinsic negative charge but also serum proteins associated on the surface play an important role in hepatic uptake of negatively charged particles via scavenger receptors.
Furumoto
Kentaro
K
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-Naka, Okayama 700-8530, Japan.
Nagayama
Susumu
S
Ogawara
Ken-Ichi
K
Takakura
Yoshinobu
Y
Hashida
Mitsuru
M
Higaki
Kazutaka
K
Kimura
Toshikiro
T
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D049329:Nanostructures; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger
D001798:Blood Proteins; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger