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

• Published in: Journal of biomedical materials research. Part B, Applied biomaterials Applied biomaterials, 2014-01, Vol.102 (1), p.190-202
• Main Authors: Swet, Jacob H., Pacheco, Hernando J., Iannitti, David A., El-Ghanam, Ahmed, McKillop, Iain H.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Biocompatibility; Biological and medical sciences; Biomedical materials; Calcium Phosphates - administration & dosage; Calcium Phosphates - chemistry; Cell Line, Tumor; chemotherapy; Cisplatin - administration & dosage; Cisplatin - pharmacokinetics; drug delivery; Drug Delivery Systems; Drug Implants - chemistry; Drugs; Gastroenterology. Liver. Pancreas. Abdomen; hepatocellular carcinoma; Injections, Intralesional; Injections, Intraperitoneal; Liver Neoplasms, Experimental - drug therapy; Liver Neoplasms, Experimental - pathology; Liver Neoplasms, Experimental - physiopathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Materials research; Materials science; Medical sciences; Microscopy, Electron, Scanning; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); nanocomposite; Nanocomposites - administration & dosage; Nanocomposites - chemistry; Nanocomposites - ultrastructure; Nanostructure; Rats; Rats, Inbred ACI; scaffold; Silicates - administration & dosage; Silicates - chemistry; Spectroscopy, Fourier Transform Infrared; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgical implants; Technology. Biomaterials. Equipments; Tissue Distribution; Toxicity; Tumors
• ISSN: 1552-4973; 1552-4981
• DOI: 10.1002/jbm.b.32995

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.