Marcella Lanza

Doxorubicin coupled to lactosaminated human albumin remains confined within mouse liver cells after the intracellular release from the carrier

BACKGROUND The hepatocyte receptor for asialoglycoproteins, which binds and internalises galactosyl terminating peptides, was found to be expressed also on the cells of the majority of hepatocarcinomas. AIMS To verify whether doxorubicin coupling to lactosaminated albumin, a galactosyl terminating neoglycoprotein, produces selective drug accumulation in hepatocytes with reduced concentrations in extra-hepatic tissues, thus facilitating the use of the drug in hepatocarcinoma treatment. METHODS Doxorubicin concentrations were measured in organs of mice injected with the free or coupled drug. RESULTS In mice injected with the coupled drug, the ratios between doxorubicin concentrations in liver and those in heart, intestine, spleen and kidney were 8-14 times higher than in animals that received the same dose of the free drug. CONCLUSIONS Due to the very efficient liver targeting of doxorubicin, the lactosaminated human albumin-doxorubicin conjugate appears to have the potential of improving the chemotherapy of hepatocellular carcinomas through the asialoglycoprotein receptor.

Liver-targeted doxorubicin: effects on rat regenerating hepatocytes.

Abstract: Background/Aims: The conjugate of doxorubicin (DOXO) with lactosaminated human albumin (L‐HSA) has the potential of improving DOXO efficacy in the treatment of hepatocellular carcinomas (HCCs) expressing the asialoglycoprotein receptor (ASGP‐R). In view of an adjuvant chemotherapy with L‐HSA–DOXO after the surgical removal of the tumour, in the present experiments we verified whether DOXO accumulation produced by the conjugate can impair the liver regeneration following hepatic resection in non‐cirrhotic liver.

Enhanced uptake of lactosaminated human albumin by rat hepatocarcinomas: implications for an improved chemotherapy of primary liver tumors

Background/Aims: The hepatocyte receptor for asialoglycoproteins (ASGP‐R) internalizes macromolecules exposing galactosyl residues (MEGRs) which can be used as liver‐addressed drug carriers. This receptor was also found on the cells of the large majority of well differentiated hepatocarcinomas (HCCs). The aim of the present experiments was to ascertain whether ASGP‐R of HCCs is functionally active and these tumors can internalize higher quantities of MEGRs than extra‐hepatic tissues.