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.
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.
UR - http://www.scopus.com/inward/record.url?scp=0036339419&partnerID=8YFLogxK
U2 - 10.1081/LPR-120004790
DO - 10.1081/LPR-120004790
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.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 -