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

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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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