UC San Diego

This thesis describes the fabrication, chemical modification, toxicity studies, and drug loading of nanostructured porous silicon for the purposes of developing a drug delivery device applied to epithelial ovarian carcinoma. The first chapter is an introductory chapter, presenting the premise of the overall research problem, the statement of purpose, and a list of questions to be understood. The second chapter focuses on a review of the relevant literature and describes the chemical and physical properties of porous silicon, the concepts and issues of current drug delivery devices and materials, applications in ovarian cancer therapeutics, and how porous silicon can address the issues regarding localized and controlled drug therapies. The third chapter explores the use of porous silicon as a material that can be delivered intraperitoneally and addresses the limitations in toxicity that can arise. Due to the toxicity, the surface of the porous silicon nanostructure can be chemically modified and rinsed to control the rate of degradation into orthosilicic acid. This chapter defines the dose range of these particles that can be delivered IP as well as discusses the effect of modifying surface chemistry to reduce toxicity. In chapter four, the concept of loading porous silicon microparticles with a therapeutic is demonstrated. The particles are loaded with cisplatin, an anti-cancer drug through a reaction instigated by the intrinsic properties of the material, trapping the drug into the pores by coating the surface with a platinum metal. Release and high localized delivery towards human ovarian cancer cells compared to free drug is discussed. The last chapter of the thesis presents a new method for attaching LyP-1 targeting peptide to porous Si microparticles for delivery towards ovarian cancer. Still much work needs to be completed in this area with regards to the targeting of LyP-1 in ovarian tumors. However, in this chapter we have demonstrated proof-of- concept that the peptide can be attached via thiol - platinum chemistry on the cisplatin loaded microparticles. The appendices mainly focus on the use of porous Si / polymer composites formed by templating to utilize the unique properties of both materials. The optical reflectivity pattern of porous Si is imprinted into mono- disperse polymer beads in the first appendix, and the second addresses the use of a malleable polymer to attempt to demonstrate a change in optical properties of the composite structure due to mechanical deformation