Enhanced liver targeting of 5-fluorouracil using galactosylated human serum albumin as a carrier molecule

The objective of this study was to develop a liver-specific antihepatocarcinoma agent. The galactosylated human serum albumin 5-fluorouracil conjugate (GHSA-5-FU) was prepared and tested for its chemical characteristic, biodistribution and primary cytotoxicity. The matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was applied to determined the molar ratio (moles of 5-FU/mole of G-HSA and moles of galactose/mole of HSA) of the conjugate. The liver targeting ability of GHSA-5-FU labeled by (131)I was evaluated by measuring the total radioactivity in organs after i.v. administration in mice and rabbits, and the cytotoxicity of the conjugate was assayed by MTT method. The results showed that the molar ratio of galactose to HSA was 50, and the 5-FU to GHSA was 15. Liver uptake in rabbits and mice peaked within 5-20 min after injection. The radioactivity (counts/g tissue) of the conjugate in the liver was several times higher than those in the other organs. The conjugate showed strong cytotoxicity, but no significant cytotoxicity difference was found between GHSA-5-FU and free 5-FU.