Mechanisms of hepatic disposition of polystyrene microspheres in rats: Effects of serum depend on the sizes of microspheres

Ken ichi Ogawara, Minoru Yoshida, Jun ichi Kubo, Makiya Nishikawa, Yoshinobu Takakura, Mitsuru Hashida, Kazutaka Higaki, Toshikiro Kimura

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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°C, respectively. However, pre-heating at 56°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°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. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)241-250
Number of pages10
JournalJournal of Controlled Release
Volume61
Issue number3
DOIs
Publication statusPublished - Sep 20 1999

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Keywords

  • Dysopsonin
  • Hepatic uptake
  • Liver perfusion
  • Opsonin
  • Polystyrene microsphere

ASJC Scopus subject areas

  • Pharmaceutical Science

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