Abstract |
Hepatocellular carcinoma (HCC) is notoriously difficult to treat with systemic chemotherapy. The aim of this study was to evaluate a silica-calcium-phosphate nanocomposite (SCPC75) drug delivery system (DDS) as a means to localize cisplatin treatment within the tumor, while reducing systemic toxicity, in a rat model of HCC. The SCPC75 was prepared and loaded with cisplatin and Fourier transform infrared analyses demonstrated even drug distribution within the SCPC75. A rat model of subcutaneous HCC formation was established and animals treated by either systemic cisplatin injection (sCis) or with SCPC75-Cis hybrid placed adjacent (ADJ) to or within (IT) the tumor. Five days after implantation, 50-55% of the total cisplatin loaded had been released from the SCPC75-Cis hybrids resulting in an approximately 50% decrease in tumor volume compared with sCis treatment. sCis-treated animals exhibited severe side effects, including rapid weight loss and decreased liver and kidney function, effects not observed in SCPC75-Cis-treated animals. Analysis of cisplatin distribution demonstrated drug concentrations in the tumor were 21 and 1.5 times higher in IT and ADJ groups, respectively, compared with sCis-treated animals. These data demonstrate the SCPC75 DDS can provide an effective, localized treatment for HCC with significantly reduced toxicity when compared with systemic drug administration.
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Authors | Jacob H Swet, Hernando J Pacheco, David A Iannitti, Ahmed El-Ghanam, Iain H McKillop |
Journal | Journal of biomedical materials research. Part B, Applied biomaterials
(J Biomed Mater Res B Appl Biomater)
Vol. 102
Issue 1
Pg. 190-202
(Jan 2014)
ISSN: 1552-4981 [Electronic] United States |
PMID | 23913418
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Wiley Periodicals, Inc. |
Chemical References |
- Antineoplastic Agents
- Calcium Phosphates
- Drug Implants
- Silicates
- silica-calcium phosphate nanocomposite
- Cisplatin
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Topics |
- Animals
- Antineoplastic Agents
(administration & dosage, pharmacokinetics)
- Calcium Phosphates
(administration & dosage, chemistry)
- Cell Line, Tumor
- Cisplatin
(administration & dosage, pharmacokinetics)
- Drug Delivery Systems
- Drug Implants
(chemistry)
- Injections, Intralesional
- Injections, Intraperitoneal
- Liver Neoplasms, Experimental
(drug therapy, pathology, physiopathology)
- Male
- Microscopy, Electron, Scanning
- Nanocomposites
(administration & dosage, chemistry, ultrastructure)
- Rats
- Rats, Inbred ACI
- Silicates
(administration & dosage, chemistry)
- Spectroscopy, Fourier Transform Infrared
- Tissue Distribution
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