Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 133-141 |
| Number of pages | 9 |
| Journal | Journal of Controlled Release |
| Volume | 97 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - May 31 2004 |
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Keywords
- Hepatic uptake
- Poly inosinic acid (poly I)
- Polystyrene nanosphere
- Receptor-mediated phagocytosis
- Scavenger receptor
- Serum opsonins
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Hepatic uptake of negatively charged particles in rats : Possible involvement of serum proteins in recognition by scavenger receptor. / Furumoto, Kentaro; Nagayama, Susumu; Ogawara, Ken Ichi; Takakura, Yoshinobu; Hashida, Mitsuru; Higaki, Kazutaka; Kimura, Toshikiro.
In: Journal of Controlled Release, Vol. 97, No. 1, 31.05.2004, p. 133-141.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hepatic uptake of negatively charged particles in rats
T2 - Possible involvement of serum proteins in recognition by scavenger receptor
AU - Furumoto, Kentaro
AU - Nagayama, Susumu
AU - Ogawara, Ken Ichi
AU - Takakura, Yoshinobu
AU - Hashida, Mitsuru
AU - Higaki, Kazutaka
AU - Kimura, Toshikiro
PY - 2004/5/31
Y1 - 2004/5/31
N2 - 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.
AB - 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.
KW - Hepatic uptake
KW - Poly inosinic acid (poly I)
KW - Polystyrene nanosphere
KW - Receptor-mediated phagocytosis
KW - Scavenger receptor
KW - Serum opsonins
UR - http://www.scopus.com/inward/record.url?scp=2442488710&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2442488710&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2004.03.004
DO - 10.1016/j.jconrel.2004.03.004
M3 - Article
C2 - 15147811
AN - SCOPUS:2442488710
VL - 97
SP - 133
EP - 141
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1
ER -