Porous silicon in drug delivery devices and materials☆
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
References (198)
- et al.
Porous silicon layers used for gas sensor applications
Thin Solid Films
(1997) - et al.
Calcium phosphate nucleation on porous silicon: factors influencing kinetics in acellular simulated body fluids
Thin Sol. Films
(1997) - et al.
Inclusion of ibuprofen in mesoporous templated silica: drug loading and release property
Eur. J. Pharm. Biopharm.
(2004) - et al.
Porous silicon as drug carrier for controlled delivery of doxorubicin anticancer agent
Microelectron. Eng.
(2006) - et al.
Mesoporous silicon in drug delivery applications
J. Pharm. Sci.
(2008) - et al.
Immobilization of urease on vapour phase stain etched porous silicon
Process Biochem.
(2007) - et al.
Enhanced in vitro permeation of furosemide loaded into thermally carbonized mesoporous silicon (TCPSi) microparticles
Eur. J. Pharm. Biopharm.
(2007) - et al.
Mesoporous silicon microparticles for oral drug delivery: loading and release of five model drugs
J. Control. Release
(2005) - et al.
Optical properties of porphyrin molecules immobilized in nano-porous silicon
Biomol. Eng.
(2007) - et al.
Fluorescence and O-1(2) generation properties of porphyrin molecules immobilized in oxidized nano-porous silicon matrix
J. Photochem. Photobiol. A—Chem.
(2006)
Dielectric filters made of porous silicon: advanced performance by oxidation and new layer structures
Thin Sol. Films
Stain films on silicon
J. Phys. Chem. Solids
The culture of neurons on silicon
Sens. Actuators A
Silicon nanostructures from electroless electrochemical etching
Curr. Opin. Solid State Mat. Sci.
Integration of porous silicon chips in an electronic artificial nose
Sens. Actuators B
Porous silicon: from luminescence to LEDs
Phys. Today
Stable electroluminescence from reverse biased n-type porous silicon–aluminum Schottky junction device
Appl. Phys. Lett.
Light-emitting porous silicon diode with an increased electroluminescence quantum efficiency
Appl. Phys. Lett.
Current-induced light emission from a porous Si device
IEEE Elec. Dev. Lett.
Smart dust: nanostructured devices in a grain of sand
Chem. Commun.
Porous silicon microcavities for biosensing applications
Phys. Status Solidi A—Appl. Res.
Porous silicon as a substrate material for potentiometric biosensors
Meas. Sci. Technol.
A porous silicon-based optical interferometric biosensor
Science
A porous silicon optical biosensor: detection of reversible binding of IgG to a protein A-modified surface
J. Am. Chem. Soc.
Porous silicon-based scaffolds for tissue engineering and other biomedical applications
Phys. Status Solidi A—Appl. Mat.
Bioactive polycrystalline silicon
Adv. Mater.
The effects of DC electric currents on the in-vitro calcification of bioactive Si wafers
Adv. Mater.
Bioactive silicon structure fabrication through nanoetching techniques
Adv. Mater.
Engineering the chemistry and nanostructure of porous silicon Fabry–Pérot films for loading and release of a steroid
Langmuir
Routes to calcifled porous silicon: implications for drug delivery and biosensing
Phys. Status Solidi A—Appl. Res.
Microfabricated porous silicon particles enhance paracellular delivery of insulin across intestinal Caco-2 cell monolayers
Pharm. Res.
Enzyme immobilization in porous silicon: quantitative analysis of the kinetic parameters for glutathione-S-transferases
Anal. Chem.
Enzyme immobilization on porous silicon surfaces
Adv. Mater.
Hydrolysis of acetylcholinesterase inhibitors - organophosphorus acid anhydrolase enzyme immobilization on photoluminescent porous silicon platforms
Chem. Commun.
Delivery of nanogram payloads using magnetic porous silicon microcarriers
Lab Chip
Cross-correlation of optical microcavity biosensor response with immobilized enzyme activity
Insights into Biosensor Sensitivity. Anal. Chem.
Quantatitive assessment of enzyme immobilization capacity in porous silicon
Anal. Chem.
Interference elimination in glutamate monitoring with chip integrated enzyme microreactors
Electroanalysis
The properties of porous silicon as a therapeutic agent via the new photodynamic therapy
J. Mater. Chem.
Photosensitized generation of singlet oxygen
Photochem. Photobiol.
Properties of porous silicon
Morphology and formation mechanisms of porous silicon
J. Electrochem. Soc.
Porous silicon formation: a quantum wire effect
Appl. Phys. Lett.
Porous Si: quantum sponge structures grown via a self-adjusting etching process
Adv. Mater.
Optical properties of porous silicon superlattices
Appl. Phys. Lett.
Application to optical components of dielectric porous silicon multilayers
Appl. Phys. Lett.
Dissolution of different forms of partially porous silicon wafers under simulated physiological conditions
Phys. Status Solidi A—Appl. Res.
Porous silicon photonic crystals as encoded microcarriers
Adv. Mater.
Microfabrication of freestanding porous silicon particles containing spectral barcodes
Phys. Status Solidi—Rapid Res. Lett.
Porous silicon-based polymer replicas formed by bead patterning
Phys. Status Solidi A—Appl. Mater.
Cited by (745)
Catalytic innovations: Improving wastewater treatment and hydrogen generation technologies
2024, Journal of Environmental ManagementMicroneedle-based cell delivery and cell sampling for biomedical applications
2023, Journal of Controlled ReleaseThe processes behind drug loading and release in porous drug delivery systems
2023, European Journal of Pharmaceutics and BiopharmaceuticsPolymer-based responsive structural color materials
2023, Progress in Materials SciencePorous silicon used as glucose detector without functionalization process: One possible alternative as sensor
2023, International Journal of Electrochemical Science
- ☆
This review is part of the Advanced Drug Delivery Reviews theme issue on “Inorganic Nanoparticles in Drug Delivery”.