This thesis describes the fabrication, chemical modification, drug release, and toxicity studies of nanostructured porous silicon for the purposes of developing a smart drug delivery device.The first chapter is an introductory chapter, presenting the chemical and physical properties of porous silicon, the concepts and issues of current drug delivery devices and materials, and how porous silicon can address the issues regarding localized and controlled drug therapies. The second chapter discusses chemical modifications of nanostructured porous Si for stabilizing the material in biologically relevant media while providing an extended release of a therapeutic in vitro. This chapter also demonstrates the utility of the porous silicon optical signatures for effectively monitoring drug release from the system and its applications for development of a self-reporting drug delivery device. In chapter three, the concept of providing a triggered release of a therapeutic from porous silicon microparticles through initiation by an external stimulus is demonstrated. The microparticles are chemically modified, and the release is enhanced by a short application of ultrasound to the particulate system. The effect of ultrasound on the drug release and particle size is discussed. Chapter four presents a new method for sustaining the release of a monoclonal antibody from the porous matrix of porous SiO2. The therapeutic is incorporated into the films through electrostatic adsorption and a slow release is observed in vitro. A new method of quantifying the extent of drug loading is monitored with interferometry. The last chapter of the thesis provides a basic in vivo toxicity study of various porous Si microparticles for intraocular applications. Three types of porous Si particles are fabricated and studied in a rabbit eye model. The toxicity studies were conducted by collaborators at the Shiley Eye Center, La Jolla, CA. This work, demonstrates the feasibility of developing a self-reporting, extended release drug delivery system using porous Si microparticles for intraocular 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.