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  • Title: Liver cancer targeting of Doxorubicin with reduced distribution to the heart using hematoporphyrin-modified albumin nanoparticles in rats.
    Author: Chang JE, Shim WS, Yang SG, Kwak EY, Chong S, Kim DD, Chung SJ, Shim CK.
    Journal: Pharm Res; 2012 Mar; 29(3):795-805. PubMed ID: 21971829.
    Abstract:
    PURPOSE: To evaluate the usefulness of hematoporphyrin (HP)-modification of the surface of doxorubicin (DOX)-loaded bovine serum albumin (BSA) nanoparticles (NPs) in the liver cancer-selective delivery of DOX. METHODS: HP-modified NPs (HP-NPs) were prepared by conjugation of amino groups on the surface of NPs with HP, a ligand for low density lipoprotein (LDL) receptors on the hepatoma cells. In vitro cellular accumulation of DOX, in vivo biodistribution of DOX, safety, and anti-tumor efficacy were evaluated for HP-NPs. RESULTS: Cytotoxicity and accumulation of DOX were in the order of HP-NPs>NPs>solution form (SOL). Cellular uptake from HP-NPs was proportional to the expression level of LDL receptors on the cells, indicating possible involvement of LDL receptor-mediated endocytosis (RME) in uptake. The "merit index," an AUC ratio of DOX in liver (target organ) to DOX in heart (major side effect organ) following iv administration of HP-NPs to hepatoma rats, was 132.5 and 4 times greater compared to SOL and NPs, respectively. The greatest suppression of body weight decrease and tumor size increase was observed for iv-administered HP-NPs in tumor-bearing mice. CONCLUSIONS: HP modification appears to be useful in selective delivery of NP-loaded DOX to tumors.
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