(688d) Antioxidant Enzyme Loading On Mesoporous Silica to Facilitate Application of Engineered Silica in Therapeutic Drug Delivery

Ordered mesoporous silica materials have emerged as potential carriers for drug delivery due to the ability to customize their pores at a scale similar to the molecular size of therapeutic proteins. The literature in this area encompasses several in-vitro demonstrations of controlled retention and release of pharmaceuticals from silica systems. However, practical implementation of such carriers is potentially limited by the adverse health effects associated with oxidative stress (whether induced by silica itself or associated with a particular disease state). In order to facilitate the use of silica in a wide range of drug delivery applications, we hypothesize that loading silica nano-particles with anti-oxidant enzymes is a viable way to curb reactive oxygen species that may potentially be associated with the use of silica. In the present study, our objective is to correlate the structural parameters of engineered silica carriers (pore size, surface area, and particle size) with the residency requirements and deactivation time of the anti-oxidant enzyme. To accomplish this, we compare loading, activity and retention of catalase on various engineered mesoporous silica ranging from non-porous to silica designed with pores large enough to freely accommodate catalase. We study resistance to proteolysis of supported catalase by pronase. We also verify our hypothesis with the help of in vivo oxidative stress measurements before and after catalase loading. The results of this study will have a useful impact on existing therapeutic applications while addressing a potential roadblock in the practical use of silica carriers.