title: Evaluation of a bioresorbable drug delivery system for the treatment of hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) represents a major global health burden. Typically HCC responds poorly to chemotherapy, and such approaches to treat HCC are commonly associated with severe hepatic and/or systemic toxicity. The aim of this study was to evaluate a porous resorbable silica-calcium phosphate nanocomposite (SCPC) as a controlled release vehicle for cisplatin. Particles of two different formulations--SCPC50 and SCPC75, containing 19.49 and 32.9 mol % silica, respectively--were loaded with cisplatin by immersion treatment and pressed into discs. In vitro release kinetics studies of cisplatin from SCPC50 and SCPC75 demonstrated an initial burst release of 0.39 ± 0.04 mg (of the 1.49 mg total loaded) and 0.87 ± 0.07 mg (of the 2.34 mg total loaded), respectively. Over the following 44-day period. SCPC75-cisplatin hybrid produced a significantly higher sustained cisplatin release than that released from SCPC50. Cisplatin release correlated well with the surface area, and silica dissolution kinetics of the SCPC carrier. Treatment of rat HCC cells (H4IIE) with cisplatin released from SCPC-cisplatin hybrids induced apoptotic cell death in H4IIE cells in vitro. Results of this study suggest that SCPC composites may be of potential use for the treatment of HCC in vivo.
authors: Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, North Carolina 28223.
authors: Kumar
authors: K
authors: Vedantham
authors: Jacob H
authors: JH
authors: Swet
authors: Iain H
authors: IH
authors: McKillop
authors: Ahmed
authors: A
authors: El-Ghannam
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D007700:Kinetics; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D016062:Porosity; D051381:Rats; D017640:Silicates / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D017640:Silicates; C499768:silica-calcium phosphate nanocomposite; D020169:Caspases; D002945:Cisplatin