Designing porous silicon-based microparticles as carriers for controlled delivery of mitoxantrone dihydrochloride
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The Inter-Departmental Program of Biotechnology, Technion – Israel Institute of Technology, Haifa 32000, Israel
Anna Rubinskia)
Department of Biotechnology and Food Engineering, Technion – Israel Institute of Technology, Haifa 32000, Israel
Ester Segalb)
Department of Biotechnology and Food Engineering, Technion – Israel Institute of Technology, Haifa 32000, Israel; and The Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa 32000, Israel (Received 11 June 2012; accepted 21 August 2012)
Porous silicon (PSi) microparticles are designed as tunable delivery carriers for the model anticancer drug, mitoxantrone dihydrochloride (MTX). The surface of the native nanostructured PSi particles was chemically modified by grafting dodecyl and undecanoic acid via thermal hydrosilylation with 1-dodecene and undecylenic acid, respectively. Attenuated total reflectance Fourier transform infrared spectroscopy and nitrogen adsorption–desorption measurements were used to characterize the physiochemical properties of the native and chemically modified PSi microparticles. MTX was loaded by physical adsorption to the native and dodecyl-terminated PSi or by covalent attachment to the undecanoic acid-terminated microparticles. Both drug release profile and the Si erosion of the carriers were significantly affected by the surface chemistry of the PSi microparticles and the drug loading method. The MTX release spans over a period of several hours to weeks, as dictated by these parameters. In vitro cytotoxicity studies on human breast carcinoma (MDA-MB-231) cells revealed that the released MTX maintains its cytotoxic functionality, in comparison to the very low toxicity of all PSi microparticles.
I. INTRODUCTION
Nanostructured porous silicon (PSi) has emerged as a promising material for biomedical applications over the past several years,1 specifically for the design of drug delivery systems.2–9 PSi is characterized by several particularly appealing features predestining it for design of drug delivery platforms: (i) high internal volume to accommodate a wide range of payloads; (ii) large surface area (up to 800 m2/g) that can be functionalized by a wide repertoire of chemical and biological species using various reactions, including silanization and hydrosilylation; (iii) inexpensive and rapid fabrication techniques with ability to further process into thin membranes and micro- or nanoparticles; (iv) biocompatibility and degradability in physiological fluids into nontoxic orthosilicic acid [Si(OH)4], which is the natural form of Si found in the body.1,10,11 Moreover, as crucial parameter in the design of erodible biomaterials relies on the ability to program their in vivo performance and retention time,12 it was demonstrated that the behavior of
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These authors contributed equally to this work. Address all correspondence to this author. e-mail: [email protected] DOI: 10.1557/jmr.2012.299 b)
J. Mater. Res., Vol. 28, No. 2, Jan 28, 2013
http://journals.cambridge.org
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