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European Journal of Nanomedicine

Editor-in-Chief: Hunziker, Patrick / Mollenhauer, Jan

Managing Editor: Löffler, Beat / Salieb-Beugelaar, Georgette

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The role of thromboxane A2 in complement activation-related pseudoallergy

Tamás Gyula Fülöp
  • Corresponding author
  • Nanomedicine Research and Education Center, Semmelweis University, 1089 Budapest, Nagyvárad tér 4, Hungary, E-mail:
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Josbert M. Metselaar
  • Department of Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, The Netherlands
  • Institute for Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, Aachen, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Gert Storm
  • Department of Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, The Netherlands
  • Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ János Szebeni
  • Nanomedicine Research and Education Center, Department of Pathophysiology, Semmelweis University, Budapest, Hungary
  • Nanomedicine Research and Education Center, Department of Pathophysiology, Semmelweis University, SeroScience Ltd, Budapest, Hungary
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-04-04 | DOI: https://doi.org/10.1515/ejnm-2016-0039


Complement activation-related pseudoallergy (CARPA) is a hypersensitivity reaction occurring upon intravenous administration of numerous liposomal therapeutics, other nonbiological complex drugs and biologicals. It has a complex molecular and cellular mechanism that involves the production, actions and interactions of numerous vasoactive mediators in blood, including thromboxane A2 (TXA2). This short review focuses on the latter eicosanoid: its role in CARPA, effects underlying some of the symptoms and experimental evidence for its rate-limiting role in pulmonary hypertension in pigs. Animal experiments and recent clinical observations suggest that the cyclooxygenase blocker indomethacin may represent an effective new approach to prevent liposome-induced CARPA, lending clinical relevance to better understand the involvement of TXA2 and other eicosanoids in this adverse immune effect.

Keywords: adverse drug reactions; allergy; anaphylatoxins; anaphylaxis; animal models; hemodynamic changes; hypersensitivity reactions; immune toxicity; pseudoallergy


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About the article

Tamás Gyula Fülöp

Tamás Gyula Fülöp, BS, PhD Student, Nanomedicine Research and Education Center, Semmelweis University, Budapest 1089 Nagyvárad tér 4, Budapest, Hungary fulopgyulatamas@gmail.com, and MIRA Institute, Department of Targeted Therapeutics, University of Twente, Enschede, The Netherlands. Gyula Tamás Fülöp is a PhD student at the Nanomedicine Research and Education Center at Semmelweis Medical University of Budapest, Hungary. He got his bachelor and master’s degree in Medical and Pharmaceutical Biotechnology at the University of Applied Sciences in Krems, Austria.

Josbert M. Metselaar

Josbert M. Metselaar, Pharm D, MIRA Institute, Department of Targeted Therapeutics, University of Twente, Enschede, The Netherlands. Josbert M. Metselaar (Rotterdam, July 6th 1971) obtained an MSc degree in Pharmaceutical Sciences in 1995 and a Pharm D (Doctor of Pharmacy) degree in 1998, both at Utrecht University. During his study, he completed a research internship in pharmacology and PK/PD modeling at the Department of Pharmaceutics, University of Florida, USA. In 1999, he started his PhD at the Department of Pharmaceutics and the Department of Immunology Veterinary Medicine in Utrecht within the scope of a large academic research collaboration funded by the Japanese pharmaceutical company Yamanouchi (nowadays Astellas). He studied novel targeted formulations of anti-inflammatory compounds in autoimmune diseases. After completing his PhD in 2003 and a postdoctoral fellowship in the same field of research in 2005, he decided to focus on translating his academic accomplishments into novel clinical and industrial investigational products. To this end, he founded his own university spin off company Enceladus Pharmaceuticals, with which he raised significant funding over the years.

Gert Storm

Gert Storm, PhD, Professor, MIRA Institute, Department of Targeted Therapeutics, University of Twente, Enschede, The Netherlands, and Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutics, Utrecht University, Utrecht, The Netherlands. Gert Storm is a (bio)pharmaceutical scientist at Utrecht University. He studied biology and obtained his PhD at the Department of Pharmaceutics of the same university. His research interests are in the fields of biopharmaceutics and drug targeting. In his early career, he worked at Liposome Technology Inc. (USA), at the San Francisco (UCSF) School of Pharmacy and at Pharma Bio-Research Consultancy B.V. (The Netherlands). In September 1991, he took up his position at Utrecht University. In 1999, he was appointed adjunct professor at the Royal School of Pharmacy, University of Copenhagen, and since 2009, he is Honorary Professor in Biomacromolecular Drug Delivery at that same university. In 2000, he was appointed as a professor (Targeted Drug Delivery) at Utrecht University. Since 2012, he is also professor (Targeted Therapeutics) at the MIRA institute of the University of Twente (Netherlands). Besides, he keeps a position at the University Medical Center Utrecht (UMCU) within the Centre for Image-Guided Oncological Interventions.

János Szebeni

Janos Szebeni, MD, PhD, DSc, Med. Habil., immunologist, director of the Nanomedicine Research and Education Center at Semmelweis University, Budapest, Hungary. He is also a professor of immunology and biology at the University of Miskolc and founder and CEO of an immune toxicology contract research biotech company, SeroScience Ltd., Hungary. During his 40-year professional career, he has held various junior, senior scientific and (guest) professor positions in Hungary and abroad, mainly in the United States, where he lived for 21 years. His research on various themes in hematology, membrane biology and immunology has resulted in over 120 papers and many book chapters, patents and a book titled The Complement System: Novel Roles in Health and Disease (Kluwer, 2004). Three fields stand out where he has been most active: artificial blood, liposomes and the complement system. His original works from the late 1990s led to the “CARPA” concept, i.e. that complement activation underlies numerous (nano)drug-induced hypersensitivity (infusion) reactions.

Received: 2016-12-19

Accepted: 2017-02-28

Published Online: 2017-04-04

Published in Print: 2017-04-01

Conflict of interest statement: Authors state no conflict of interest. All authors have read the journal’s publication ethics and publication malpractice statement available at the journal’s website and hereby confirm that they comply with all its parts applicable to the present scientific work.

Citation Information: European Journal of Nanomedicine, Volume 9, Issue 2, Pages 59–67, ISSN (Online) 1662-596X, ISSN (Print) 1662-5986, DOI: https://doi.org/10.1515/ejnm-2016-0039.

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