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J Hepatol. 2005 Oct;43(4):645-52.

Doxorubicin coupled to lactosaminated albumin inhibits the growth of hepatocellular carcinomas induced in rats by diethylnitrosamine.

Author information

  • 1Department of Experimental Pathology, University of Bologna, via San Giacomo, 14 40126 Bologna, Italy. luigi.fiume@unibo.it

Abstract

BACKGROUND/AIMS:

The hepatocyte receptor for asialoglycoproteins internalizes galactosyl terminating macromolecules which can be used as hepatotropic drug carriers. Since this receptor is also expressed on the cells of well differentiated human hepatocellular carcinomas (HCCs), we studied whether conjugation of doxorubicin (DOXO) with lactosaminated human albumin (L-HSA) increases the drug efficacy on HCCs induced in rats by diethylnitrosamine (DENA).

METHODS:

DENA was given in the drinking water for 8 weeks. One week after the last day of DENA administration, animals were randomly assigned to three groups. Each group was administered with either saline, free or coupled DOXO (1 microg/g). Rats received 4 weekly intravenous injections. One week after the last administration, rats were killed and HCC development was evaluated by counting the tumor nodules on the surface of hepatic lobes.

RESULTS:

In rats treated with L-HSA coupled DOXO the number of neoplastic nodules was significantly lower (P < 0.05) than that counted in animals injected with saline or with free DOXO. Coupled DOXO did not decrease body rat weight, which was markedly reduced by the free drug.

CONCLUSIONS:

Conjugation with L-HSA increased the antineoplastic efficacy and decreased the systemic toxicity of DOXO administered to rats with HCCs produced by DENA.

PMID:
16023760
DOI:
10.1016/j.jhep.2005.02.045
[PubMed - indexed for MEDLINE]
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