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A silica-calcium-phosphate nanocomposite drug delivery system for the treatment of hepatocellular carcinoma: in vivo study.

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.
AuthorsJacob H Swet, Hernando J Pacheco, David A Iannitti, Ahmed El-Ghanam, Iain H McKillop
JournalJournal 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
PMID23913418 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Wiley Periodicals, Inc.
Chemical References
  • Antineoplastic Agents
  • Calcium Phosphates
  • Drug Implants
  • Silicates
  • silica-calcium phosphate nanocomposite
  • Cisplatin
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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