UC San Diego

The sustained delivery of therapeutics with minimal systemic side effects would be a benefit in the treatment of many diseases. Numerous nanostructured materials in various shapes and sizes have been investigated to meet this challenge. This dissertation focuses in particular on the development of nanostructured porous silicon-based materials for observable and sustained drug delivery. Previously, drugs loaded into porous silicon particles resulted in rapid drug release. In order to improve upon drug release kinetics, loading of drugs into porous silicon particles by physical adsorption and covalent attachment were compared, and the mechanism of drug release was studied. We found that drug loading by covalent attachment was able to eliminate burst release and provide extended drug release compared to previous results. One area that can benefit from such a sustained drug release system is ocular drug delivery. In this work, we investigated the use of porous silicon particles loaded with drug by covalent attachment for its potential in the treatment of the retina. Drug release was studied in a custom designed flow chamber designed to mimic the half- life of drugs in the human vitreous, and sustained drug release of up to one month was observed. In addition, the optical properties of porous silicon was used to monitor drug release. An area of concern in using porous silicon as drug delivery carriers is the reactivity between porous silicon and redox active drug molecules such as anthracyclines. We demonstrate that reactive surface hydrides on porous silicon can reduce anthracyclines and create potential toxicity. However, we show that thermal oxidation can be used as a means to prevent this reduction. Finally, the degradation and toxicity of porous silicon and silica particles were studied in vivo using a rabbit eye model. We demonstrate that porous silicon and silica particles loaded with drugs are biocompatible. In addition, the color of the particles can be readily observed by a fundus camera, showing its potential as an indicator of drug release. These studies illustrate the possibility of using porous silicon based particles as a self reporting drug carrier for the long-term release of therapeutics