Elsevier

Advanced Drug Delivery Reviews

Volume 60, Issue 11, 17 August 2008, Pages 1266-1277
Advanced Drug Delivery Reviews

Porous silicon in drug delivery devices and materials

https://doi.org/10.1016/j.addr.2008.03.017Get rights and content

Abstract

Porous Si exhibits a number of properties that make it an attractive material for controlled drug delivery applications: The electrochemical synthesis allows construction of tailored pore sizes and volumes that are controllable from the scale of microns to nanometers; a number of convenient chemistries exist for the modification of porous Si surfaces that can be used to control the amount, identity, and in vivo release rate of drug payloads and the resorption rate of the porous host matrix; the material can be used as a template for organic and biopolymers, to prepare composites with a designed nanostructure; and finally, the optical properties of photonic structures prepared from this material provide a self-reporting feature that can be monitored in vivo. This paper reviews the preparation, chemistry, and properties of electrochemically prepared porous Si or SiO2 hosts relevant to drug delivery applications.

Introduction

Porous Si has been investigated for applications in microelectronics, optoelectronics, [1], [2], [3], [4] chemical [5], [6] and biological [7], [8], [9], [10] sensors, and biomedical devices [11]. The in vivo use of porous Si was first promoted by Leigh Canham, who demonstrated its resorbability and biocompatibility in the mid 1990s [12], [13], [14], [15]. Subsequently, porous Si or porous SiO2 (prepared from porous Si by oxidation) host matrices have been employed to demonstrate in vitro release of the steroid dexamethasone [16], ibuprofen [17], cis-platin [18], doxorubicin [19], and many other drugs [20]. The first report of drug delivery from porous Si across a cellular barrier was performed with insulin, delivered across monolayers of Caco-2 cells [21]. An excellent review of the potential for use of porous Si in various drug delivery applications has recently appeared [20].

An emerging theme in porous Si as applied to medicine has been the construction of microparticles (“mother ships”) with sizes on the order of 1–100 μm that can carry a molecular or nanosized payload, typically a drug. With a free volume that can be in excess of 80%, porous Si can carry cargo such as proteins, enzymes [22], [23], [24], [25], [26], [27], [28], [29], drugs [16], [17], [18], [19], [20], [30], [31], or genes. It can also carry nanoparticles, which can be equipped with additional homing devices, sensors, or cargoes. In addition, the optical properties of nanocrystalline silicon can be recruited to perform various therapeutic or diagnostic tasks—for example, quantum confined silicon nanostructures can act as photosensitizers to produce singlet oxygen as a photodynamic therapy [32], [33], [34], [35]. A long-term goal is to harness the optical, electronic, and chemical properties of porous Si that can allow the particles to home to diseased tissues such as tumors and then perform various tasks in vivo. These tasks include detecting, identifying, imaging, and delivering therapies to the tissue of interest. In this work we review the chemistry of porous Si that allows the incorporation of drug payloads, homing devices, optical features for imaging, and sensors for detection of various physical changes.

Section snippets

Electrochemical etching

Porous Si is a product of an electrochemical anodization of single crystalline Si wafers in a hydrofluoric acid electrolyte solution. Pore morphology and pore size can be varied by controlling the current density, the type and concentration of dopant, the crystalline orientation of the wafer, and the electrolyte concentration in order to form macro-, meso-, and micropores [36]. Pore sizes ranging from 1 nm to a few microns can be prepared.

The mechanism of pore formation is not generally agreed

Biocompatibility and reactions of biological relevance

Silicon is an essential trace element that is linked to the health of bone and connective tissues [51]. The chemical species of relevance to the toxicity of porous Si are silane (SiH4) and dissolved oxides of silicon; three important chemical reactions of these species are given in Eq. (1), (2), (3). The surface of porous Si contains Si–H, SiH2, and SiH3 species that can readily convert to silane [52], [53]. Silane is chemically reactive (Eq. (1)) and toxic, especially upon inhalation [54], [55]

Loading and controlled release of drugs with porous Si

Providing a controlled and localized release of therapeutics within the body are key objectives for increasing efficacy and reducing the risks of potential side effects [115], [116], [117], [118], [119]. The low toxicity of porous Si and porous SiO2, the high porosity, and the relatively convenient surface chemistry has spurred interest in the use of this system as a host, or “mother ship” for therapeutics, diagnostics, or other types of payloads. Various approaches to load a molecular payload

Composites of porous Si and polymers

Hybrid materials, in which the payload consists of an organic polymer or a biopolymer, forms an additional class of host/payload systems. Composites are attractive candidates for drug delivery devices because they can display a combination of advantageous chemical and physical characteristics not exhibited by the individual constituents. Advances in polymer [136] and materials [137] chemistries have greatly expanded the design options for nanomaterial composites in the past few years, and

In vivo monitoring using the optical properties of porous Si

Many material hosts have been developed for drug delivery, but few can ‘self-report’ on the amount of drug loaded or released. It is important to know these quantities when determining the efficacy of a treatment to identify when it is time to administer a new dose. The unique optical properties that can be engineered into porous Si provide a mechanism to perform such assays in vivo. Incorporation of molecules into a porous Si layer alters its index of refraction, and the spectrum obtained from

Medical applications of porous Si

The suitability and efficacy of various forms of porous Si are being assessed for medical applications, and some are currently in clinical trials. The incorporation of anti-cancer therapeutics [19], [181], anti-inflammatory agents [16], [31], analgesics [31], and medicinally relevant proteins and peptides has been demonstrated [21]. The oral administration of porous Si to provide a dietary supplement of silicon [182] has also been assessed [183]. Porous Si drug delivery devices have taken the

Summary and prospects

Porous Si microparticles offer a number of properties of interest for controlled drug delivery: First, nanostructured materials based on silicon are promising platforms for pharmaceutical applications because they provide low toxicity. Their ability to degrade in the body presents fewer challenges for chronic use than, for example, carbon nanotubes which are not metabolized and so must be excreted after administration.

Second, the electrochemical means of fabrication allows one to “dial in” the

Acknowledgements

The authors thank Dr. Sadik Esener, Dr. Stephen Howell, Dr. Danielle Jandial, Dr. Jean-Marie Devoioselle, Dr. Frederique Cunin, Jennifer Park, and Elizabeth Wu for helpful discussions. Financial support from the National Science Foundation, grant # DMR-0503006 (MJS), NIH grant EYO-7366 (WRF) and Research to Prevent Blindness, Inc. (WRF) is gratefully acknowledged. MJS is a member of the Moores UCSD Cancer Center and the UCSD NanoTUMOR Center under which this research was conducted and partially

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