Targeting liver tumors by administering liposomal doxorubicin into the hepatic artery

Yiyu Zou, Isamu Horikoshi, Masaharu Ueno, Xueqiu Gu, Roman Perez‐Soler

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The plasma levels, organ distribution, and in vivo anti‐tumor activity of liposomal doxorubicin administered i.v. or i.a. (hepatic) in rats bearing W256 liver tumors were studied. I.a. administration of liposomal doxorubicin resulted in 4‐fold and 1.3‐fold higher liver tumor and liver parenchyma doxorubicin levels, respectively, than i.v. administration, thus suggesting a more preferential distribution of liposomal doxorubicin into the liver tumor with i.a. administration. By contrast, the heart, spleen, and plasma AUCs were decreased 3.8‐, 3.2‐, and 16‐fold, respectively, after i.a. administration. Cumulative urinary excretion at 8 hr was also 14 times lower in animals that received liposomal doxorubicin i.a. In good correlation with these findings, i.a. administration markedly enhanced the anti‐tumor effect of liposomal doxorubicin against liver W256 tumors as measured by tumor growth inhibition 5 days after treatment (‐16% for i.a. administration vs. +89% for i.v. administration, p ⩽ 0.05) and prolongation of survival (ILS: 108% for i.a. administration vs. 26% for i.v. administration, p ⩽ 0.05). Our results show that i.a. administration of liposomal doxorubicin results in preferential distribution of the anti‐tumor agent into the tumor tissue and increased anti‐tumor activity, while increasing the cardioprotective effect of the liposome carrier by decreasing the plasma peak and heart‐tissue levels of the drug.

Original languageEnglish (US)
Pages (from-to)232-237
Number of pages6
JournalInternational Journal of Cancer
Volume51
Issue number2
DOIs
StatePublished - May 8 1992
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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