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 SiO 2 hosts relevant to drug delivery applications.

Fluorescence imaging is one of the most versatile and widely used visualization methods in biomedical research. However, tissue autofluorescence is a major obstacle confounding interpretation of in vivo fluorescence images. The unusually long emission lifetime (5-13 μs) of photoluminescent porous silicon nanoparticles can allow the time-gated imaging of tissues in vivo, completely eliminating shorter-lived (< 10 ns) emission signals from organic chromophores or tissue autofluorescence.Here, using a conventional animal imaging system not optimized for such long-lived excited states, we demonstrate improvement of signal to background contrast ratio by > 50-fold in vitro and by > 20-fold in vivo when imaging porous silicon nanoparticles. Time-gated imaging of porous silicon nanoparticles accumulated in a human ovarian cancer xenograft following intravenous injection is demonstrated in a live mouse. The potential for multiplexing of images in the time domain by using separate porous silicon nanoparticles engineered with different excited state lifetimes is discussed.

A method for engineering the surface chemistry and pore dimensions in porous Si films for the purpose of controlling the loading and release of a hydrophobic drug is described. Loading of the steroid dexamethasone is confirmed by Fourier transform infrared spectroscopy, and the release rates are characterized by observation of the appearance of the drug in solution (UV-vis absorption spectroscopy) and by measurement of the Fabry-Perot fringes in the optical reflectivity spectrum of the porous Si film. Optical reflectivity changes provide a measure of the release rate of the drug that is amenable to in-vivo diagnostic applications. Fresh porous Si films are prepared by electrochemical etch and subsequently modified by hydrosilylation with 1-dodecene. The dodecene-modified samples are more robust in aqueous environments and exhibit slower release rates of the drug relative to freshly etched porous Si. Whereas the relatively large dexamethasone molecule is found to infiltrate the freshly etched samples, it does not enter the chemically modified films, because of steric crowding from the dodecyl species. To achieve a high degree of loading into these modified films, the pores are enlarged before hydrosilylation by treatment with an aqueous solution containing HF and dimethyl sulfoxide. The pore expanded, chemically modified samples admit approximately 70% of the dexamethasone that can be admitted into an unmodified (freshly etched) sample. Diffusion of the steroid from the modified, pore expanded films into phosphate-buffered saline solution is slower than from the unmodified sample by a factor of approximately 20, with 90% of the drug delivered in 3 days for the chemically modified films compared to 3 h for the unmodified films.

Aim-To determine the suitability of porous silicon photonic crystals for intraocular drug-delivery.Methods-A rugate structure was electrochemically etched into a highly doped p-type silicon substrate to create a porous silicon film that was subsequently removed and ultrasonically fractured into particles. To stabilise the particles in aqueous media, the silicon particles were modified by surface alkylation (using thermal hydrosilylation) or by thermal oxidation. Unmodified particles, hydrosilylated particles and oxidised particles were injected into rabbit vitreous. The stability and toxicity of each type of particle were studied by indirect ophthalmoscopy, biomicroscopy, tonometry, electroretinography (ERG) and histology.Results-No toxicity was observed with any type of the particles during a period of >4 months. Surface alkylation led to dramatically increased intravitreal stability and slow degradation. The estimated vitreous half-life increased from 1 week (fresh particles) to 5 weeks (oxidised particles) and to 16 weeks (hydrosilylated particles). Conclusion-The porous silicon photonic crystals showed good biocompatibility and may be used as an intraocular drug-delivery system. The intravitreal injectable porous silicon photonic crystals may be engineered to host a variety of therapeutics and achieve controlled drug release over long periods of time to treat chronic vitreoretinal diseases.There is an important medical need for a minimally invasive, controllable and monitorable drug-delivery system that would enable long-acting local treatment of intraocular diseases affecting the retina and choroid. In particular, diseases such as choroidal neovascularisation (CNV) in age-related macular degeneration (ARMD), proliferative vitreoretinopathy (PVR) associated with retinal detachment and trauma, and refractory uveitis would benefit greatly. For those chronic refractory diseases, drug delivery to the vitreous, retina and choroid is a challenging task due to the formidable obstacles posed by the blood-retinal barrier and the tight junctions of the retinal pigment epithelium. With systemic administration, only small fractions of drug reach the target, requiring large and potentially toxic doses. An ideal method of retinal drug delivery would provide a locally sustained release for prolonged periods of time. Due to the short vitreous half-life of most injectable intravitreal drugs, frequent administrations are necessary. Intravitreal injection has become standard in clinical practice and trials; however, We have investigated self-assembling liposomes and, most recently, a crystalline drug-delivery material to achieve intraocular long-lasting release of selected antiviral and antiproliferative compounds. 3 4 In particular, the lipid prodrug-delivery system is not feasible for delivery of large molecular compounds such as polypeptides and proteins, which are becoming increasingly important in the treatment of eye diseases. Other systems consisting of biodegradable and bioerodible polymeric microparticles have...

Nanostructured mesoporous silica (SiO 2 ) films are used to load and release the monoclonal antibody bevacizumab (Avastin) in vitro. A biocompatible and biodegradable form of mesoporous SiO 2 is prepared by electrochemical etching of single crystalline Si, followed by thermal oxidation in air at 800 °C. Porous SiO 2 exhibits a negative surface charge at physiological pH (7.4), allowing it to spontaneously adsorb the positively charged antibody from an aqueous phosphate buffered saline solution. This electrostatic adsorption allows bevacizumab to be concentrated by >100× (300 mg bevacziumab per gram of porous SiO 2 when loaded from a 1 mg mL −1 solution of bevacziumab). Drug loading is monitored by optical interferometric measurements of the thin porous film. A two-component Bruggeman effective medium model is employed to calculate percent porosity and film thickness, and is further used to determine the extent of drug loading into the porous SiO 2 film. In vitro drug release profiles are characterized by an enzyme-linked immunosorbent assay (ELISA), which confirms that the antibody is released in its active, VEGFbinding form. The nanostructured delivery system described here provides a sustained release of the monoclonal antibody where approximately 98% of drug is released over a period of one month.