Abstract | PURPOSE: Undesirable complement (C) activation by nanomedicines can entail an adverse immune reaction known as C activation-related pseudoallergy (CARPA) in sensitive patients. The syndrome includes cardiopulmonary, hemodynamic, and a variety of other physiological changes that have been well described in man, pigs, dogs, and rats. However, the information on CARPA is scarce and ambiguous in mice, a species widely used in preclinical studies. The present study aimed to fill this gap by exploring signs of CARPA in mice following i.v. administration of AmBisome and Abelcet, which are nano-formulations of Amphotericin B with high risk to cause CARPA. MATERIALS AND METHODS: RESULTS: CONCLUSION: The parallelism between C3a anaphylatoxin production and severity of physiological changes caused by the different agents is consistent with CARPA underlying these changes. Although the reactive dose of liposomal phospholipids was substantially higher than that in other species (pigs, dogs), the mouse seems suitable for studying the mechanism of hypersensitivity reactions to liposomal formulations of amphotericin B, a frequent side effect of these drugs.
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Authors | Erik Őrfi, Tamás Mészáros, Mark Hennies, Tamás Fülöp, László Dézsi, Alexander Nardocci, László Rosivall, Péter Hamar, Barry W Neun, Marina A Dobrovolskaia, János Szebeni, Gábor Szénási |
Journal | International journal of nanomedicine
(Int J Nanomedicine)
Vol. 14
Pg. 1563-1573
( 2019)
ISSN: 1178-2013 [Electronic] New Zealand |
PMID | 30880965
(Publication Type: Journal Article)
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Chemical References |
- Liposomes
- Receptors, Complement
- complement C3a receptor
- liposomal amphotericin B
- Amphotericin B
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Topics |
- Amphotericin B
(pharmacology)
- Animals
- Blood Pressure
(drug effects)
- Complement Activation
(drug effects)
- Heart Rate
(drug effects)
- Hemodynamics
(drug effects)
- Hypertension
(physiopathology)
- Immunity, Innate
(drug effects)
- Liposomes
- Male
- Mice, Inbred C57BL
- Physiological Phenomena
(drug effects)
- Receptors, Complement
(antagonists & inhibitors, metabolism)
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