Lactosaminated human albumin, a hepatotropic carrier of drugs.

A selective delivery of drugs to liver can be obtained by conjugation with galactosyl terminating macromolecules. The conjugates selectively enter hepatocytes after interaction of the carrier galactose residues with the asialoglycoprotein receptor (ASGP-R) present only on these cells. Within hepatocytes the conjugates are transported to lysosomes where the drug is set free from the carrier, becoming concentrated in liver cells. The present article reviews the liver targeting of drugs obtained with lactosaminated albumin (L-SA), a neoglycoprotein exposing galactosyl residues. We report: (1) experiments which demonstrate the antiviral efficacy of the L-H(human)SA-ara-AMP conjugate in laboratory animals and in humans with viral hepatitis; (2) the property of a L-HSA conjugate with fluorodeoxyuridine to produce concentrations of the drug higher in hepatic sinusoids than in systemic circulation, with the potential of accomplishing a loco-regional, noninvasive treatment of liver micrometastases; (3) the increased anticancer activity of doxorubicin (DOXO) when coupled to L-HSA on all the forms of chemically induced rat hepatocellular carcinomas including those which do not express the ASGP-R.