title: Comparison of complement activation-related pseudoallergy in miniature and domestic pigs: foundation of a validatable immune toxicity model.
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.
  
  
  BACKGROUND
  With the advances in nanomedicine research, many new agents are now tested for use in clinical setting. Nonetheless, complement activation-related pseudoallergy (CARPA) is a well known phenomenon which can be caused by nanoparticles. In this study, the authors looked at and compared the use of domestic pigs versus miniature pigs as experimental animals for toxicological studies. Their findings confirmed the possible use of miniature pigs for regulatory testing.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore; Centre for Biomimetic Sensor Science, Nanyang Technological University, Singapore.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Jackman
authors.affiliation: Nanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Nagyvárad tér 4. Budapest, Hungary; SeroScience Ltd, Nagyvárad tér 4. Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Mészáros
authors.affiliation: Nanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Nagyvárad tér 4. Budapest, Hungary; SeroScience Ltd, Nagyvárad tér 4. Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Fülöp
authors.affiliation: Nanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Nagyvárad tér 4. Budapest, Hungary; SeroScience Ltd, Nagyvárad tér 4. Budapest, Hungary.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Urbanics
authors.affiliation: Nanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Nagyvárad tér 4. Budapest, Hungary; SeroScience Ltd, Nagyvárad tér 4. Budapest, Hungary; Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health Science, Miskolc University, Miskolc, Hungary. Electronic address: jszebeni2@gmail.com.
authors.forename: Janos
authors.initials: J
authors.lastname: Szebeni
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore; Centre for Biomimetic Sensor Science, Nanyang Technological University, Singapore; School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore. Electronic address: njcho@ntu.edu.sg.
authors.forename: Nam-Joon
authors.initials: NJ
authors.lastname: Cho
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D003167:Complement Activation; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004342:Drug Hypersensitivity; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D008081:Liposomes / Q000009:adverse effects*; D050997:Nanomedicine; D053758:Nanoparticles / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D013552:Swine; D013556:Swine, Miniature; D015054:Zymosan / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D008081:Liposomes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; C000515:cremophor EL; D000666:Amphotericin B; D004317:Doxorubicin; D015054:Zymosan; D005990:Glycerol
keywords: CARPA; Immune toxicity; Infusion reactions; Miniature pig; Regulatory standards