Comparison of complement activation-related pseudoallergy in miniature and domestic pigs: Foundation of a validatable immune toxicity model

Joshua A. Jackman, T. Mészáros, Tamás Fülöp, Rudolf Urbanics, J. Szebeni, Nam Joon Cho

Research output: Article

23 Citations (Scopus)

Abstract

Complement activation-related pseudoallergy (CARPA) is an acute adverse immune reaction caused by many nanomedicines. There is a regulatory need for a sensitive and standardizable in vivo predictive assay. While domestic pigs are a sensitive animal model, miniature pigs are favored in toxicological studies yet their utility as a CARPA model has not yet been explored. Herein, we used liposomal doxorubicin and amphotericin B (Doxil/Caelyx and AmBisome), Cremophor EL and zymosan as CARPA triggers to induce reactions in miniature and domestic pigs, and compared the hemodynamic, hematological, biochemical, and skin alterations. The changes observed after administration of the test agents were very similar in both pig strains, suggesting that miniature pigs are a sensitive, reproducible, and, hence, validatable animal model for CARPA regulatory testing.

Original languageEnglish
Pages (from-to)933-943
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume12
Issue number4
DOIs
Publication statusPublished - máj. 1 2016

Fingerprint

Sus scrofa
Complement Activation
Toxicity
Chemical activation
Swine
Animals
Animal Models
Antigen-antibody reactions
Nanomedicine
Medical nanotechnology
Zymosan
Hemodynamics
Amphotericin B
Toxicology
Assays
Skin
Testing
liposomal doxorubicin
liposomal amphotericin B

ASJC Scopus subject areas

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

Cite this

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abstract = "Complement activation-related pseudoallergy (CARPA) is an acute adverse immune reaction caused by many nanomedicines. There is a regulatory need for a sensitive and standardizable in vivo predictive assay. While domestic pigs are a sensitive animal model, miniature pigs are favored in toxicological studies yet their utility as a CARPA model has not yet been explored. Herein, we used liposomal doxorubicin and amphotericin B (Doxil/Caelyx and AmBisome), Cremophor EL and zymosan as CARPA triggers to induce reactions in miniature and domestic pigs, and compared the hemodynamic, hematological, biochemical, and skin alterations. The changes observed after administration of the test agents were very similar in both pig strains, suggesting that miniature pigs are a sensitive, reproducible, and, hence, validatable animal model for CARPA regulatory testing.",
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T2 - Foundation of a validatable immune toxicity model

AU - Jackman, Joshua A.

AU - Mészáros, T.

AU - Fülöp, Tamás

AU - Urbanics, Rudolf

AU - Szebeni, J.

AU - Cho, Nam Joon

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KW - Infusion reactions

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KW - Regulatory standards

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