Complement activation by PEGylated liposomes containing prednisolone

Jolanda M. Van Den Hoven, Reka Nemes, Josbert M. Metselaar, Bastiaan Nuijen, Jos H. Beijnen, Gert Storm, Janos Szebeni

Research output: Contribution to journalArticle

37 Citations (Scopus)


Infusion of PEGylated liposomes can give rise to hypersensitivity reactions (HSRs) in a relatively large number of patients. Previously it has been shown that these reactions can be caused by activation of the complement (C) system by a negative charge on the anchor molecule of PEG at the liposomal surface. In this study it is tested whether the activation of the C system by PEG-liposomes could be significantly reduced to values comparable to nonreactive liposomal formulations, by changing the PEGylation-profile on the liposomal surface. Therefore, the formation of C activation markers SC5b-9, C3a, C4d and Bb in normal human serum by both prednisolone loaded and empty liposomes with a variation of PEG chain length, PEG surface concentration, PEG anchor molecule and liposomal size was determined using in vitro assays. The tested liposomes caused no or only mild (30%) activation of C except for one formulation wherein the PEG2000 was anchored to cholesterol (CHOL-PEG2000). The latter liposomes caused paralleling rises in SC5b-9 and Bb levels, suggesting excess activation of the alternative pathway. While the relative safety of weak C activator liposomes remains to be confirmed in vivo, the unique, non-charge and non-antibody-mediated direct conversion of C3 by CHOL-PEG2000 liposomes (although argues against the clinical development of these vesicles) opens new opportunities to understand liposomal C activation at the molecular level.

Original languageEnglish
Pages (from-to)265-271
Number of pages7
JournalEuropean Journal of Pharmaceutical Sciences
Issue number2
Publication statusPublished - May 13 2013



  • Complement activation
  • Hypersensitivity reactions
  • Infusion reactions
  • PEGylated liposomes

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Van Den Hoven, J. M., Nemes, R., Metselaar, J. M., Nuijen, B., Beijnen, J. H., Storm, G., & Szebeni, J. (2013). Complement activation by PEGylated liposomes containing prednisolone. European Journal of Pharmaceutical Sciences, 49(2), 265-271.