title: Engineering porous silicon nanostructures as tunable carriers for mitoxantrone dihydrochloride.
abstract: Nanostructured porous silicon (PSi) thin films, fabricated by the electrochemical anodization of single crystalline Si wafers, are studied as delivery systems for the anticancer drug mitoxantrone dihydrochloride (MTX). The surface chemistry of the PSi carriers was tailored by surface alkylation using thermal hydrosilylation of 1-dodecene and undecylenic acid, followed by physical adsorption or covalent attachment of MTX to the Si scaffold. The nanostructure and the physiochemical properties of the different carriers were characterized by attenuated total reflectance Fourier transform infrared spectroscopy, nitrogen adsorption-desorption and contact angle measurements, demonstrating that surface alkylation results in a pronounced effect on the hydrophobicity/hydrophilicity of the scaffolds and a volumetric gain in pore wall, which in turn results in a decrease in pore diameter (>23%) and available porous volume (>40%). The effect of these key parameters on MTX loading efficacy, release profile, Si scaffold erosion kinetics and in vitro cytotoxicity on human breast carcinoma (MDA-MB-231) cells was studied and compared to the behavior of neat PSi carriers. We show that the chemically modified PSi carriers exhibit sustained release for several days to weeks with minimal to no burst effect, while for the native PSi MTX release was completed within 5h with a substantial burst release of ~40%. Moreover, our in vitro cytotoxicity experiments have clearly demonstrated that the MTX released from all PSi carriers maintained its cytotoxic effect towards MDA-MB-231 cells, in comparison to the low toxicity of the PSi carriers.
authors.affiliation: The Interdepartmental Program of Biotechnology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Tzur-Balter
authors.forename: Ariel
authors.initials: A
authors.lastname: Gilert
authors.forename: Naama
authors.initials: N
authors.lastname: Massad-Ivanir
authors.forename: Ester
authors.initials: E
authors.lastname: Segal
mesh_terms: D000042:Absorption; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004058:Diffusion; D006801:Humans; D008422:Materials Testing; D008942:Mitoxantrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D016062:Porosity; D012825:Silicon / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D053769:Nanocapsules; C055847:mitoxantrone dicarboxylic acid; D008942:Mitoxantrone; D012825:Silicon