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. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 190–202, 2014.