title: 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.
authors.affiliation: Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina, 28203.
authors.forename: Jacob H
authors.initials: JH
authors.lastname: Swet
authors.forename: Hernando J
authors.initials: HJ
authors.lastname: Pacheco
authors.forename: David A
authors.initials: DA
authors.lastname: Iannitti
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Ghanam
authors.forename: Iain H
authors.initials: IH
authors.lastname: McKillop
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002130:Calcium Phosphates / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004343:Drug Implants / Q000737:chemistry; D015552:Injections, Intralesional; D007274:Injections, Intraperitoneal; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D053761:Nanocomposites / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D051381:Rats; D011912:Rats, Inbred ACI; D017640:Silicates / Q000008:administration & dosage* / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D002130:Calcium Phosphates; D004343:Drug Implants; D017640:Silicates; C499768:silica-calcium phosphate nanocomposite; D002945:Cisplatin
keywords: chemotherapy; drug delivery; hepatocellular carcinoma; nanocomposite; scaffold