Role of complement activation in hypersensitivity reactions to Doxil and HYNIC PEG liposomes: Experimental and clinical studies

J. Szebeni, L. Baranyi, S. Savay, J. Milosevits, R. Bunger, P. Laverman, J. M. Metselaar, G. Storm, A. Chanan-Khan, L. Liebes, F. M. Muggia, R. Cohen, Y. Barenholz, C. R. Alving

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

Pegylated liposomal doxorubicin (Doxil) and 99mTc-HYNIC PEG liposomes (HPL) were reported earlier to cause hypersensitivity reactions (HSRs) in a substantial percentage of patients treated i.v. with these formulations. Here we report that (1) Doxil, HPL, pegylated phosphati-dylethanolamine (PEG-PE)-containing empty liposomes matched with Doxil and HPL in size and lipid composition, and phosphatidylglycerol (PG)-containing negatively charged vesicles were potent C activators in human serum in vitro, whereas small neutral liposomes caused no C activation. (2) Doxil and other size-matched PEG-PE and/or PG-containing liposomes also caused massive cardiopulmonary distress with anaphylactoid shock in pigs via C activation, whereas equivalent neutral liposomes caused no hemodynamic changes. (3) A clinical study showed more frequent and greater C activation in patients displaying HSR than in non-reactive patients. These data suggest that liposome-induced HSRs in susceptible individuals may be due to C activation, which, in turn, is due to the presence of negatively charged PEG-PE in these vesicles.

Original languageEnglish (US)
Pages (from-to)165-172
Number of pages8
JournalJournal of Liposome Research
Volume12
Issue number1-2
DOIs
StatePublished - Aug 15 2002

ASJC Scopus subject areas

  • Pharmaceutical Science

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