Liposome-induced hypersensitivity reactions

Risk reduction by design of safe infusion protocols in pigs

Tamás Fülöp, G. Kozma, Ildikó Vashegyi, T. Mészáros, L. Rosivall, Rudolf Urbanics, Gert Storm, Josbert M. Metselaar, J. Szebeni

Research output: Contribution to journalArticle

Abstract

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
Volume309
DOIs
Publication statusPublished - Sep 10 2019

Fingerprint

Risk Reduction Behavior
Liposomes
Hypersensitivity
Swine
Prednisolone
Thromboxane B2
Pharmaceutical Preparations
Nanomedicine
Pulmonary Hypertension
Intravenous Administration
Heart Rate
Hemodynamics
Blood Pressure
Lung

Keywords

  • Anaphylatoxins
  • CARPA
  • Complement
  • Infusion reaction
  • Nanomedicines
  • Nanoparticle
  • Nanopharmaceuticals
  • PEGylation
  • Pseudoallergy

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Liposome-induced hypersensitivity reactions : Risk reduction by design of safe infusion protocols in pigs. / Fülöp, Tamás; Kozma, G.; Vashegyi, Ildikó; Mészáros, T.; Rosivall, L.; Urbanics, Rudolf; Storm, Gert; Metselaar, Josbert M.; Szebeni, J.

In: Journal of Controlled Release, Vol. 309, 10.09.2019, p. 333-338.

Research output: Contribution to journalArticle

Fülöp, Tamás ; Kozma, G. ; Vashegyi, Ildikó ; Mészáros, T. ; Rosivall, L. ; Urbanics, Rudolf ; Storm, Gert ; Metselaar, Josbert M. ; Szebeni, J. / Liposome-induced hypersensitivity reactions : Risk reduction by design of safe infusion protocols in pigs. In: Journal of Controlled Release. 2019 ; Vol. 309. pp. 333-338.
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