Liver cancer targeting of Doxorubicin with reduced distribution to the heart using hematoporphyrin-modified albumin nanoparticles in rats.

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.

• Authors: Ji-Eun Chang, Won-Sik Shim, Su-Geun Yang, Eun-Young Kwak, Saeho Chong, Dae-Duk Kim, Suk-Jae Chung, Chang-Koo Shim
• Journal: Pharmaceutical research (Pharm Res) Vol. 29 Issue 3 Pg. 795-805 (Mar 2012) ISSN: 1573-904X [Electronic] United States
• PMID: 21971829 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Hematoporphyrins
• Serum Albumin, Bovine
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics, therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cattle
• Doxorubicin (administration & dosage, pharmacokinetics, therapeutic use)
• Drug Delivery Systems (methods)
• Hematoporphyrins (chemistry)
• Hep G2 Cells
• Humans
• Liver (drug effects, pathology)
• Liver Neoplasms (drug therapy, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Myocardium (metabolism)
• Nanoparticles (chemistry)
• Rats
• Rats, Sprague-Dawley
• Serum Albumin, Bovine (chemistry)