Linked Life Data

20966743

Source:http://linkedlifedata.com/resource/pubmed/id/20966743

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-12-23
pubmed:abstractText
Galactosyl-terminated drug carriers are known to enhance drug accumulation in the liver, while possible accompanying hepatic toxicity is usually not clarified. This study developed a galactosyl-?,?-poly[(2-hydroxyethyl)-L-aspartamide]-doxorubicin conjugate (Gal-PHEA-DOX) and investigated its therapeutic efficacy and safety in orthotopic hepatocellular carcinoma-bearing mice. Gal-PHEA-DOX had a galactosylation degree of 7.5 mol% and a DOX content of 8.9 wt%. A biodistribution study showed that Gal-PHEA-DOX sustainedly circulated in the plasma and highly accumulated in hepatocarcinoma. Free drug liberated from Gal-PHEA-DOX was relatively low in the liver and heart as compared with that of the DOX administration. The Gal-PHEA-DOX conjugate showed superior cytotoxicity against the hepatocellular carcinoma cell line HepG2 as compared with the nongalactosylated PHEA-DOX conjugate. Gal-PHEA-DOX exhibited comparable antitumor activity with PHEA-DOX in the S180-bearing mice, but more effective than PHEA-DOX or DOX in the Heps-bearing mice with negligible detrimental effect in the liver remnant. A systemic toxicity study showed that this conjugate did not show either cytotoxicity or hepatotoxicity at a relatively high dose, which would be harmful for free DOX. These results suggest that the Gal-PHEA-DOX conjugate has great potential for use in hepatocellular carcinoma chemotherapy because of its enhanced antitumor effect with reduced systemic toxicity including hepatotoxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1473-5741
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
136-47
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Galactosylated ?,?-poly[(2-hydroxyethyl)-L-aspartamide]-bound doxorubicin: improved antitumor activity against hepatocellular carcinoma with reduced hepatotoxicity.
pubmed:affiliation
Department of Polymer Science and Engineering, Nanjing University, Nanjing, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't