Genomic perspectives in inter-individual adverse responses following nanomedicine administration: The way forward

The underlying mechanism of intravenous infusion-related adverse reactions inherent to regulatory-approved nanomedicines still remains elusive. There are substantial inter-individual differences in observed adverse reactions, which may include cardiovascular, broncho-pulmonary, muco-cutaneous, neuro...

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Bibliographic Details
Published in:Advanced drug delivery reviews 2012-10, Vol.64 (13), p.1385-1393
Main Authors: Moghimi, S. Moein, Wibroe, Peter P., Helvig, Shen Y., Farhangrazi, Z. Shadi, Hunter, A. Christy
Format: Article
Language:English
Subjects:
Acute allergic-like reactions
Anaphylatoxins
Animals
Autonomic nervous system
C3a receptor
C5a receptor
Complement system
Drug-Related Side Effects and Adverse Reactions
Gene expression
Genomics
Humans
Infusions, Intravenous - adverse effects
Nanomedicine
Pharmaceutical Preparations - administration & dosage
Polymorphism, Genetic
Single nucleotide polymorphism
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Summary:The underlying mechanism of intravenous infusion-related adverse reactions inherent to regulatory-approved nanomedicines still remains elusive. There are substantial inter-individual differences in observed adverse reactions, which may include cardiovascular, broncho-pulmonary, muco-cutaneous, neuro-psychosomatic and autonomic manifestations. Although nanomedicine-mediated triggering of complement activation has been suggested to be a significant contributing factor to these adverse events, complement activation may still proceed in non-responders. Whether these reactions share similar immunological mechanisms and underpinning genetic factors with drug hypersensitivity syndrome remains to be investigated. Genetic association studies could be a powerful tool to dissect causative factors and reveal the multiple molecular pathways that induce infusion related adverse reactions. It is envisaged that such research may lead to the design of reliable in vitro profiling tests for risk assessment and treatment decisions, thereby revolutionizing the practice of medicine with nanopharmaceuticals. Such procedures may further improve regulatory approval processes for nanomedicines currently in the pipeline and decrease the overall cost of health care. Here we discuss some key innate immunity genes and their polymorphisms in relation to nanomedicine infusion-mediated symptomatic responses. [Display omitted]
ISSN:0169-409X
1872-8294
DOI:10.1016/j.addr.2012.05.010