Document Detail


Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo.
MedLine Citation:
PMID:  17512998     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Pratik Singh; Duane Prasuhn; Robert M Yeh; Giuseppe Destito; Chris S Rae; Kent Osborn; M G Finn; Marianne Manchester
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-04-13
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  120     ISSN:  1873-4995     ISO Abbreviation:  J Control Release     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-11     Completed Date:  2007-07-26     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  41-50     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Comovirus*
Drug Carriers / administration & dosage,  chemistry,  pharmacokinetics*,  toxicity*
Heterocyclic Compounds / chemistry
Injections, Intravenous
Liver / metabolism
Mice
Mice, Inbred BALB C
Models, Molecular
Molecular Conformation
Nanoparticles*
Organometallic Compounds / chemistry
Spectrophotometry / methods
Spleen / drug effects,  metabolism,  pathology
Terbium / chemistry
Virion*
Grant Support
ID/Acronym/Agency:
R01 CA112075/CA/NCI NIH HHS; R01 CA112075/CA/NCI NIH HHS; R01 CA112075-04/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Drug Carriers; 0/Heterocyclic Compounds; 0/Organometallic Compounds; 06SSF7P179/Terbium; 92923-44-9/gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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