Journal
DRUG DISCOVERY TODAY
Volume 23, Issue 5, Pages 1034-1042Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2017.11.006
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Funding
- Danish Agency for Science, Technology and Innovation (Det Strategiske Forskningsrad) [09-065746]
- Danish Council for Independent Research, Technology and Production Sciences [12-126894, 1335-00150b]
- Lundbeckfonden [R100-A9443]
- International Science and Technology Cooperation of Guangdong Province [2015A050502002]
- Guangzhou City [2016201604030050]
- RiboBio Co, Ltd, China
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Injection/infusion reactions to nanopharmaceuticals (and particulate drug carriers) are idiosyncratic and well documented. The molecular basis of nanoparticle-mediated injection reactions is debatable, with two hypotheses as front-runners. The first is complement-activation-related 'pseudoallergy', where a causal role for nanoparticle-mediated complement activation in injection/infusion reactions is considered. However, the second hypothesis (the rapid phagocytic response hypothesis) states a transitional link from robust clearance of nanoparticles (NPs) from the blood by strategically placed responsive macrophages to adverse hemodynamic and cardiopulmonary reactions, regardless of complement activation. Here, I critically examine and discuss these hypotheses. Current experimentally derived evidence appears to be more in support of the rapid phagocytic response hypothesis than of the 'pseudoallergy' hypothesis.
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