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

141 Citations (Scopus)

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
Pages (from-to)165-172
Number of pages8
JournalJournal of Liposome Research
Volume12
Issue number1-2
DOIs
Publication statusPublished - 2002

Fingerprint

Complement Activation
Liposomes
Hypersensitivity
Phosphatidylglycerols
liposomal doxorubicin
Clinical Studies
Shock
Swine
Hemodynamics
Lipids
Serum

ASJC Scopus subject areas

  • Pharmacology

Cite this

Role of complement activation in hypersensitivity reactions to Doxil and HYNIC PEG liposomes : Experimental and clinical studies. / Szebeni, J.; Baranyi, L.; Savay, S.; Milosevits, J.; Bunger, R.; Laverman, P.; Metselaar, J. M.; Storm, G.; Chanan-Khan, A.; Liebes, L.; Muggia, F. M.; Cohen, R.; Barenholz, Y.; Alving, C. R.

In: Journal of Liposome Research, Vol. 12, No. 1-2, 2002, p. 165-172.

Research output: Contribution to journalArticle

Szebeni, J, Baranyi, L, Savay, S, Milosevits, J, Bunger, R, Laverman, P, Metselaar, JM, Storm, G, Chanan-Khan, A, Liebes, L, Muggia, FM, Cohen, R, Barenholz, Y & Alving, CR 2002, 'Role of complement activation in hypersensitivity reactions to Doxil and HYNIC PEG liposomes: Experimental and clinical studies', Journal of Liposome Research, vol. 12, no. 1-2, pp. 165-172. https://doi.org/10.1081/LPR-120004790
Szebeni, J. ; Baranyi, L. ; Savay, S. ; Milosevits, J. ; Bunger, R. ; Laverman, P. ; Metselaar, J. M. ; Storm, G. ; Chanan-Khan, A. ; Liebes, L. ; Muggia, F. M. ; Cohen, R. ; Barenholz, Y. ; Alving, C. R. / Role of complement activation in hypersensitivity reactions to Doxil and HYNIC PEG liposomes : Experimental and clinical studies. In: Journal of Liposome Research. 2002 ; Vol. 12, No. 1-2. pp. 165-172.
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