Liposome-induced complement activation and related cardiopulmonary distress in pigs: Factors promoting reactogenicity of Doxil and AmBisome

János Szebeni, Péter Bedocs, Zoltán Rozsnyay, Zsóka Weiszhár, Rudolf Urbanics, László Rosivall, Rivka Cohen, Olga Garbuzenko, György Báthori, Miklós Tóth, Rolf Bünger, Yechezkel Barenholz

Research output: Article

127 Citations (Scopus)

Abstract

Hypersensitivity reactions to liposomal drugs, often observed with Doxil and AmBisome, can arise from activation of the complement (C) system by phospholipid bilayers. To understand the mechanism of this adverse immune reaction called C activation-related pseudoallergy (CARPA), we analyzed the relationship among liposome features, C activation in human serum in vitro, and liposome-induced cardiovascular distress in pigs, a model for human CARPA. Among the structural variables (surface charge, presence of saturated, unsaturated, and PEGylated phospholipids, and cisplatin vs. doxorubicin inside liposomes), high negative surface charge and the presence of doxorubicin were significant contributors to reactogenicity both in vitro and in vivo. Morphological analysis suggested that the effect of doxorubicin might be indirect, via distorting the sphericity of liposomes and, if leaked, causing aggregation. The parallelism among C activation, cardiopulmonary reactions in pigs, and high rate of hypersensitivity reactions to Doxil and AmBisome in humans strengthens the utility of the applied tests in predicting the risk of CARPA. From the Clinical Editor: The authors studied complement activation-related pseudoallergy (CARPA) in a porcine model and demonstrate that high negative surface charge and drug effects leading to distortion of liposome sphericity might be the most critical factors leading to CARPA. The applied tests might be used to predict CARPA in humans.

Original languageEnglish
Pages (from-to)176-184
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume8
Issue number2
DOIs
Publication statusPublished - febr. 1 2012

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Liposome-induced complement activation and related cardiopulmonary distress in pigs: Factors promoting reactogenicity of Doxil and AmBisome'. Together they form a unique fingerprint.

  • Cite this