Evidence map›Paper›PMID 30880965›Full record

ArticleInternational journal of nanomedicine2019

Acute physiological changes caused by complement activators and amphotericin B-containing liposomes in mice.

Erik Őrfi, Tamás Mészáros, Mark Hennies, Tamás Fülöp, László Dézsi, Alexander Nardocci, László Rosivall, Péter Hamar, Barry W Neun, Marina A Dobrovolskaia and 2 more

Open access · goldAbstract read
In one paragraph

Article in International journal of nanomedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 25 citations in OpenAlex.

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  4. siRNA-mediated reduction of a circulating protein in swine using lipid nanoparticles.Molecular therapy. Methods & clinical development · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Erik ŐrfiNanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary, jszebeni2@gmail.com.
Tamás MészárosNanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary, jszebeni2@gmail.com.
Mark HenniesTECOdevelopment GmbH, Rheinbach, Germany.
Tamás FülöpNanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary, jszebeni2@gmail.com.
László DézsiNanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary, jszebeni2@gmail.com.
Alexander NardocciNanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary, jszebeni2@gmail.com.
László RosivallNanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary, jszebeni2@gmail.com.
Péter HamarInstitute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
Barry W NeunNanotechnology Characterization Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Marina A DobrovolskaiaNanotechnology Characterization Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA.
János SzebeniNanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary, jszebeni2@gmail.com.
Gábor SzénásiNanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary, jszebeni2@gmail.com.
Semmelweis University · HUFrederick National Laboratory for Cancer Research · US

Funding

CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

purposeUndesirable 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

methodsAnesthetized NMRI mice were intravenously injected with liposomal amphotericin B (Abelcet and AmBisome; 30-300 mg phospholipid/kg), drug-free high cholesterol multilamellar vesicles (HC-MLV), and positive controls, cobra venom factor (CVF) and zymosan, followed by the measurement of blood pressure (BP), heart rate, white blood cell, and platelet counts and plasma thromboxane B2 (TXB2) levels. C activation was assessed by C3a ELISA, a C3 consumption assay (PAN-C3) and a modified sheep red blood cell hemolytic assay.

resultsAll test agents, except HC-MLV, caused transient hypertension, thrombocytopenia, and elevation of plasma TXB2, which were paralleled by significant rises of plasma C3a in CVF and zymosan-treated animals, wherein the initial hypertension turned into hypotension and shock. Abelcet and AmBisome caused minor, delayed rise of C3a that was not associated with hypertension. The C3a receptor inhibitor SB-290157 attenuated the hypertension caused by Abelcet and decreased the BP thereafter.

conclusionThe 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.

Indexed as

Amphotericin BAnimalsBlood PressureComplement ActivationHeart RateHemodynamicsHypertensionImmunity, InnateLiposomesMaleMice, Inbred C57BLPhysiological PhenomenaReceptors, ComplementAmphotericin Bcomplement C3a receptorliposomal amphotericin BLiposomesReceptors, Complementanaphylatoxinscholesterolcobra venom factorhypersensitivityinfusion reactionsplateletsTXB2zymosan

Identifiers

PMID30880965
PMCPMC6396670
OpenAlexW2916086178

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.