Lessons learned from the porcine CARPA model

Constant and variable responses to different nanomedicines and administration protocols

Rudolf Urbanics, Péter Bedocs, J. Szebeni

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Pigs provide a sensitive and quantitative animal model of complement (C) activation-related pseudoallergy (CARPA) caused by liposomes and a wide range of nanoparticulate drugs or drug nanocarriers (nanomedicines). The tetrad of symptoms (hemodynamic, hematological, laboratory and skin changes) that arise within minutes after i.v. injection of reactogenic nanomedicines (RNMs) are highly reproducible among different pigs but the presence, direction and relative severity of symptoms are very different with different RNMs and their administration schedule. Bolus administration of RNMs usually trigger pulmonary hypertension with or without various degrees of systemic hyper- or hypotension, tachy-or bradycardia, arrhythmia, blood cell and inflammatory mediator changes and skin rash. These reactions can be rapid or protracted, and fully tachyphylactic, semi-tachyphylactic or non-tachyphylactic. Slow infusion usually diminishes the reactions and/or entail delayed, protracted and less severe hemodynamic and other changes. The goal of this review is to present some technical details of the porcine CARPA model, point out its constant and variable parameters, show examples of different reactions, highlight the unique features and capabilities of the model and evaluate its utility in preclinical safety assessment. The information obtained in this model enables the understanding of the complex pathomechanism of CARPA involving simultaneous anaphylatoxin and inflammatory mediator actions at multiple sites in different organs.

Original languageEnglish
Pages (from-to)219-231
Number of pages13
JournalEuropean Journal of Nanomedicine
Volume7
Issue number3
DOIs
Publication statusPublished - Jun 1 2015

Fingerprint

Nanomedicine
Medical nanotechnology
lessons learned
hypertension
hemodynamics
Swine
swine
Chemical activation
activation
bradycardia
hypotension
Hemodynamics
drugs
arrhythmia
blood cells
Skin
animal models
Anaphylatoxins
schedules
organs

Keywords

  • anaphylatoxins
  • anaphylaxis
  • animal models
  • hemodynamic changes
  • hypersensitivity reactions
  • pseudoallergy

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Physical and Theoretical Chemistry
  • Biomedical Engineering

Cite this

Lessons learned from the porcine CARPA model : Constant and variable responses to different nanomedicines and administration protocols. / Urbanics, Rudolf; Bedocs, Péter; Szebeni, J.

In: European Journal of Nanomedicine, Vol. 7, No. 3, 01.06.2015, p. 219-231.

Research output: Contribution to journalArticle

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