Document Detail


Liposomal delivery of doxorubicin to hepatocytes in vivo by targeting heparan sulfate.
MedLine Citation:
PMID:  19664697     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous work demonstrated that liposomes, containing an amino acid sequence that binds to hepatic heparan sulfate glycosaminoglycan, show effective targeting to liver hepatocytes. These liposomes were tested to determine whether they can deliver doxorubicin selectively to liver and hepatocytes in vivo. Fluid-phase liposomes contained a lipid-anchored 19-amino acid glycosaminoglycan targeting peptide. Liposomes were loaded with doxorubicin and were non-leaky in the presence of serum. After intravenous administration to mice, organs were harvested and the doxorubicin content extracted and measured by fluorescence intensity and by fluorescence microscopy. The liposomal doxorubicin was recovered almost entirely from liver, with only trace amounts detectable in heart, lung, and kidney. Fluorescence microscopy demonstrated doxorubicin preferentially in hepatocytes, also in non-parenchymal cells of the liver, but not in cells of heart, lung or kidney. The doxorubicin was localized within liver cell nuclei within 5 min after intravenous injection. These studies demonstrated that liposomal doxorubicin can be effectively delivered to hepatocytes by targeting the heparan sulfate glycosaminoglycan of liver tissue. With the composition described here, the doxorubicin was rapidly released from the liposomes without the need for an externally supplied stimulus.
Authors:
Kenneth J Longmuir; Sherry M Haynes; Janie L Baratta; Natasha Kasabwalla; Richard T Robertson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-08-05
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  382     ISSN:  1873-3476     ISO Abbreviation:  Int J Pharm     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-10-27     Completed Date:  2010-02-02     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  222-33     Citation Subset:  IM    
Affiliation:
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697, USA.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus
Animals
Antibiotics, Antineoplastic / blood,  chemistry,  pharmacokinetics*
Chemistry, Pharmaceutical
Doxorubicin / administration & dosage,  blood,  chemistry,  pharmacokinetics*
Drug Carriers*
Drug Compounding
Drug Stability
Female
Heparitin Sulfate / metabolism*
Hepatocytes / metabolism*
Injections, Intravenous
Liposomes
Mice
Mice, Inbred BALB C
Microscopy, Fluorescence
Nanoparticles
Peptide Fragments / administration & dosage,  chemistry,  metabolism*
Protozoan Proteins / administration & dosage,  chemistry,  metabolism*
Spectrometry, Fluorescence
Tissue Distribution
Grant Support
ID/Acronym/Agency:
EB-003075/EB/NIBIB NIH HHS; R01 EB003075-05/EB/NIBIB NIH HHS
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Drug Carriers; 0/Liposomes; 0/Peptide Fragments; 0/Protozoan Proteins; 0/circumsporozoite protein, Protozoan; 23214-92-8/Doxorubicin; 9050-30-0/Heparitin Sulfate
Comments/Corrections

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


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