Liposome-induced hypersensitivity reactions: Risk reduction by design of safe infusion protocols in pigs

Tamás Fülöp, Gergely T. Kozma, Ildikó Vashegyi, Tamás Mészáros, László Rosivall, Rudolf Urbanics, Gert Storm, Josbert M. Metselaar*, János Szebeni*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)
95 Downloads (Pure)


Intravenous administration of liposomal drugs can entail infusion reactions, also known as hypersensitivity reactions (HSRs), that can be severe and sometimes life-threatening in a small portion of patients. One empirical approach to prevent these reactions consists of lowering the infusion speed and extending the infusion time of the drug. However, different liposomal drugs have different levels of reactogenicity, which means that the optimal protocol for each liposomal drug may differ and should be identified and evaluated to make the treatment as safe and convenient as possible. The goal of the present study was to explore the use of pigs for the above purpose, using PEGylated liposomal prednisolone (PLP) as a model drug. We compared the reactogenicities of bolus versus infusion protocols involving 2-, 3- and 4-step dose escalations for a clinically relevant total dose, also varying the duration of infusions. The strength of HSRs was measured via continuous recording of hemodynamic parameters and blood thromboxane B2 levels. We showed that bolus administration or rapid infusion of PLP caused transient changes in systemic and pulmonary blood pressure and heart rate, most notably pulmonary hypertension with paralleling rises in plasma thromboxane B2. These adverse responses could be significantly reduced or eliminated by slow infusion of PLP, with the 3-h 3-step dose escalation protocol being the least reactogenic. These data suggest that the pig model enables the development of safe infusion protocols for reactogenic nanomedicines.

Original languageEnglish
Pages (from-to)333-338
Number of pages6
JournalJournal of controlled release
Publication statusPublished - 10 Sep 2019


  • UT-Hybrid-D
  • Complement
  • Infusion reaction
  • Nanomedicines
  • Nanoparticle
  • Nanopharmaceuticals
  • PEGylation
  • Pseudoallergy
  • Anaphylatoxins


Dive into the research topics of 'Liposome-induced hypersensitivity reactions: Risk reduction by design of safe infusion protocols in pigs'. Together they form a unique fingerprint.

Cite this