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Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo

Academic Article
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Overview

related to degree

  • Prasuhn Jr., Duane E, Ph.D. in Chemistry, Scripps Research 2001 - 2007

authors

  • Singh, P.
  • Prasuhn Jr., Duane E
  • Yeh, R. M.
  • Destito, G.
  • Rae, C. S.
  • Osborn, K.
  • Finn, M.G.
  • Manchester, Marianne

publication date

  • July 2007

journal

  • Journal of Controlled Release  Journal

abstract

  • Virus-based nanoparticles (VNPs) from a variety of sources are being developed for biomedical and nanotechnology applications that include tissue targeting and drug delivery. However, the fate of most of those particles in vivo has not been investigated. Cowpea mosaic virus (CPMV), a plant comovirus, has been found to be amenable to the attachment of a variety of molecules to its coat protein, as well as to modification of the coat protein sequence by genetic means. We report here the results of studies of the bio-distribution, toxicology, and pathology of CPMV in mice. Plasma clearance and tissue biodistribution were measured using CPMV particles derivatized with lanthanide metal complexes. CPMV particles were cleared rapidly from plasma, falling to undetectable levels within 20 min. By 30 min the majority of the injected VNPs were trapped in the liver and to a lesser extent the spleen with undetectable amounts in other tissues. At doses of 1 mg, 10 mg and 100 mg per kg body weight, no toxicity was noted and the mice appeared to be normal. Hematology was essentially normal, although with the highest dose examined, the mice were somewhat leukopenic with relative decreases in both neutrophils and lymphocytes. Histological examination of the spleen showed cellular infiltration, which upon flow cytometry analyses revealed elevated B lymphocytes on the first day following virus administration that subsequently subsided. Microscopic evaluation of various other tissues revealed a lack of apparent tissue degeneration or necrosis. Overall, CPMV appears to be a safe and non-toxic platform for in vivo biomedical applications.

subject areas

  • Animals
  • Comovirus
  • Drug Carriers
  • Heterocyclic Compounds
  • Injections, Intravenous
  • Liver
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Molecular Conformation
  • Nanoparticles
  • Organometallic Compounds
  • Spectrophotometry
  • Spleen
  • Terbium
  • Virion
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Research

keywords

  • biodistribution
  • cowpea mosaic vir-us
  • delivery vehicle
  • nanoparticle
  • toxicity
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Identity

PubMed Central ID

  • PMC2849971

International Standard Serial Number (ISSN)

  • 0168-3659

Digital Object Identifier (DOI)

  • 10.1016/j.jconrel.2007.04.003

PubMed ID

  • 17512998
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Additional Document Info

start page

  • 41

end page

  • 50

volume

  • 120

issue

  • 1-2

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