TY - JOUR
T1 - Role of complement activation in hypersensitivity reactions to Doxil and HYNIC PEG liposomes
T2 - Experimental and clinical studies
AU - Szebeni, J.
AU - Baranyi, L.
AU - Savay, S.
AU - Milosevits, J.
AU - Bunger, R.
AU - Laverman, P.
AU - Metselaar, J. M.
AU - Storm, G.
AU - Chanan-Khan, A.
AU - Liebes, L.
AU - Muggia, F. M.
AU - Cohen, R.
AU - Barenholz, Y.
AU - Alving, C. R.
N1 - Funding Information:
1Walter Reed Army Institute of Research, Silver Spring, MD, USA 2Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA 3Department of Nuclear Medicine, University Medical Center, Nijmegen, The Netherlands 4Utrecht Institute for Pharmaceutical Science, Utrecht University, Utrecht, The Netherlands 5Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, USA 6Laboratory of Membrane and Liposome Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1081/LPR-120004790
DO - 10.1081/LPR-120004790
M3 - Article
C2 - 12604051
AN - SCOPUS:0036339419
SN - 0898-2104
VL - 12
SP - 165
EP - 172
JO - Journal of Liposome Research
JF - Journal of Liposome Research
IS - 1-2
ER -