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  • Title: Role of complement activation in hypersensitivity reactions to doxil and hynic PEG liposomes: experimental and clinical studies.
    Author: 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.
    Journal: J Liposome Res; 2002; 12(1-2):165-72. PubMed ID: 12604051.
    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 phosphatidylethanolamine (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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