Targeting Behavior of Hepatic Artery Injected Temperature Sensitive Liposomal Adriamycin on Tumor-Bearing Rats

Yiyu Zou, Xueqiu Gu, Masaharu Ueno, Makiko Yamagishi, Isamu Horikoshi, Iwao Yamashita, Kenji Tazawa

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Temperature sensitive liposomal Adriamycin(LADM) was injected into the hepatic artery of rats bearing implanted hepatic tumors. Two hours after the injection, the liver was heated at 42 °C and maintained for six minutes at that temperature using local hyperthermia. Blood samples were taken at regular intervals until 8 hours after injection, at which time the animals were sacrificed and the drug distribution in the tissues was examined. Results indicate that the Adriamycin was released from the liposome, with the drug concentration in circulation peaking at 30 minutes after heating. High drug levels(25.2 ug/g of wet tissue) in the tumor and high tumor/liver Adriamycin level ratios(TLAR; 4.1) were found. The drug levels and the TLAR of the liposomal Adriamycin injection combined with heating (LADM H) were significantly different from those of the same dose of aqueous Adriamycin with heating(ADM H) or aqueous Adriamycin(ADM) and LADM without heating. The experiment shows that the LADM is cleared from the liver slowly, and when hyperthermia treatment at phase-transition temperature of the liposome is performed, the drug level in an implanted hepatic tumor is increased, and in the parenchyma is decreased. The results imply that targeting the hepatic tumor in this way may be an effective therapeutic method, and the drug release from the liposome may be controlled externally. This method appears promising for clinical practice.

Original languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalSelective Cancer Therapeutics
Volume6
Issue number3
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Cancer Research

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