Preclinical and clinical experience with a doxorubicin-liposome preparation

Alberto Gabizon*, Shimon Amselem, Dorith Goren, Rivka Cohen, Shulamith Druckmann, Ilana Fromer, Roland Chisin, Tamar Peretz, Aaron Sulkes, Yechezkel Barenholz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Entrapment of doxorubicin in liposomes results in increased drug concentrations in liver and spleen and decreased uptake by the heart muscle. these pharmacologic changes can be exploited to reduce the drug's toxicity and increase its therapeutic index in selected neoplastic conditions. We review here our preclinical and phase I clinical data with liposome-associated doxorubicin. these studies, together with preliminary observations on the pharmacokinetics of the liposome-associated drug and on the imaging of radiolabeled vesicles in patients, suggest that the maximal tolerated dosage is significantly increased over that of the free drug and that the reticuloendothelial system is responsible for the rapid and dominant pathway of liposome clearance. the implications of various pharmacologic aspects of liposome behavior in the circulation are also discussed.

Original languageEnglish
Pages (from-to)491-502
Number of pages12
JournalJournal of Liposome Research
Volume1
Issue number4
DOIs
StatePublished - 1990

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