Document Detail

Increased bone marrow toxicity of doxorubicin bound to nanoparticles.
MedLine Citation:
PMID:  7917543     Owner:  NLM     Status:  MEDLINE    
The in vivo myelosuppressive effects of free and polyalkylcyanoacrylate-bound doxorubicin were compared in a mouse model. After intravenous administration of 11 mg/kg body weight of doxorubicin either free or bound to polyisobutyl (doxo-PIBCA) or polyisohexylcyanoacrylate (doxo-PIHCA) nanoparticles, we studied the total and differential counts of blood, bone marrow and spleen cells; the number of granulocyte progenitors (CFU-GM) was determined by culture. Doxorubicin concentrations were measured with an HPLC method in the bone marrow and the spleen. Doxo-PIHCA nanoparticles showed the highest and longest myelosuppressive effects which correlated well with a high concentration of the drug in the bone marrow and the spleen. Moreover, it was found that PIHCA nanoparticles induced the release of colony stimulating factors, which might account for the observed increase of toxic effects of doxorubicin on bone marrow progenitors. These data also indicate that a more precise evaluation of the myelosuppressive effects of targeted formulations of anticancer drugs is needed, which may be attained by studies on bone marrow progenitors.
S Gibaud; J P Andreux; C Weingarten; M Renard; P Couvreur
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of cancer (Oxford, England : 1990)     Volume:  30A     ISSN:  0959-8049     ISO Abbreviation:  Eur. J. Cancer     Publication Date:  1994  
Date Detail:
Created Date:  1994-11-08     Completed Date:  1994-11-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9005373     Medline TA:  Eur J Cancer     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  820-6     Citation Subset:  IM    
Laboratoire de Pharmacie Galénique, U.R.A. CNRS 1218, France.
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MeSH Terms
Bone Marrow / drug effects*
Colony-Stimulating Factors / blood
Doxorubicin / administration & dosage,  adverse effects*
Drug Carriers
Femur / drug effects
Hematopoietic Stem Cells / drug effects
Leukocyte Count / drug effects
Mice, Inbred Strains
Platelet Count / drug effects
Spleen / drug effects
Reg. No./Substance:
0/Colony-Stimulating Factors; 0/Cyanoacrylates; 0/Drug Carriers; 0/Polymers; 107811-81-4/polyisohexylcyanoacrylate; 23214-92-8/Doxorubicin; 26809-38-1/polyisobutyl cyanoacrylate

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