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

S. Moein Moghimi, Peter P. Wibroe, Shen Y. Helvig, Z. Shadi Farhangrazi, A. Christy Hunter

Research output: Contribution to journalReview article

36 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1385-1393
Number of pages9
JournalAdvanced Drug Delivery Reviews
Volume64
Issue number13
DOIs
StatePublished - Oct 2012

Keywords

  • Acute allergic-like reactions
  • Anaphylatoxins
  • C3a receptor
  • C5a receptor
  • Complement system
  • Gene expression
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Pharmaceutical Science

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