Details

Autor(en) / Beteiligte

• Nakane, Sachi
• Matsumoto, Satoshi
• Takakura, Yoshinobu
• Hashida, Mitsuru
• Sezaki, Hitoshi

Titel

The Accumulation Mechanism of Cationic Mitomycin C-dextran Conjugates in the Liver: In-vivo Cellular Localization and In-vitro Interaction with Hepatocytes

Ist Teil von

• Journal of pharmacy and pharmacology, 1988-01, Vol.40 (1), p.1-6

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

1988

Quelle

MEDLINE

Beschreibungen/Notizen

• — To elucidate the mechanism of the accumulation of mitomycin C‐dextran conjugate (MMC‐D) in the liver, in‐vivo cellular uptake and in‐vitro cellular interaction of MMC‐D have been studied. Localization of cationic and anionic MMC‐D (MMC‐Dcat. and MMC‐Dan.) in different liver cell types following i.v. administration was examined in rats and the significant contribution of parenchymal cells demonstrated. In‐vitro cellular interaction was determined by measuring the drug concentration in the medium after incubation with rat isolated hepatocytes. MMC‐Dcat. was highly adsorbed on the surface of hepatocytes at pH 7.2, while the interaction between MMC‐Dan. and hepatocytes was negligible. The percentage association of MMC‐Dcat. with hepatocytes remained almost constant during the course of incubation and no significant difference was observed between the incubation at 4 and 37 °C. The adsorption phenomenon was shown to conform to Langmuir's adsorption isotherm. The amount of MMC‐Dcat. associated with hepatocytes increased as the molecular weight of the dextran chain increased. These results showed that MMC‐Dcat. was adsorbed on the surface of hepatocytes by an electrostatic force and this binding was responsible for its remarkable accumulation in the liver in‐vivo. Thus some physicochemical properties of the MMC‐D conjugates are thought to play an important role in the disposition characteristics of the conjugates.