Pore Size Dependence of Proteinase K Diffusion Through Sol-Gel Derived Silica

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0915-R01-09

Pore Size Dependence of Proteinase K Diffusion Through Sol-Gel Derived Silica Winny Dong1, Weijen Lin2, Nicole Contreras1, Doja Elmatari1, YiHsuan Lin2, and Maria Torres1 1 Chemical and Materials Engineering, California State Polytechnic University, Pomona, Pomona, 91768 2 Biological Sciences, California State Polytechnic University, Pomona, Pomona, 91768

ABSTRACT Sol-gel derived silica particles are candidates for injectable controlled drug-delivery vehicles. In this study, Proteinase K was the model biomolecule encapsulated in the silica xerogel, ambigel, and aerogel particles. The surface area and average pore diameter of these particles are reported. Both the amount of Proteinase K released from the particles and the activity of the released Proteinase K were measured as a function of time. Aerogels showed a significantly lower specific activity compared to xerogels and ambigels. A variety of factors such as surface chemistry, processing parameters, solvent interaction, and pore structures were investigated as possible causes. The primary finding of this study is the effect of pore diameter on the specific activity of Proteinase K released from these particles.

INTRODUCTION The development of controlled drug-release vehicles is one of the fastest growing fields in pharmaceutical engineering. Sol-gel derived silica, along with micelles, liposomes, dendrimers, hydrogels, and other types of polymers have been considered as likely candidates. [1-5] In some circumstances, sol-gel derived silica have been shown to have superior thermal and chemical stability among the various matrices under investigation.[1,2,6] The specific interest in forming particles arose from the effort to create drug-delivery vehicles that are injectable. Understanding diffusion characteristics and factors that affect both the diffusion and activity of the released protein is important in controlled drug delivery devices. Barbe et al. have studied the release of various drug molecules through sol-gel silica nanoparticles synthesized through the emulsion process. [7,8] Other groups have investigated various parameters such as particle size, pH, and other synthesis parameters on the diffusion of biomolecules through sol-gel derived silica particles.[9,10] Additionally, the effects of surface interactions on the activity of encapsulated biomolecules (lipases) have been reported. [11-13] However, none have looked specifically at the effects of different drying methods on both the diffusion and the level of activity retained by the released biomolecule. In this study, we investigate how different drying conditions could affect the specific activity of Proteinase K released from sol-gel derived silica particles. The sol-gel method is a low-temperature process for synthesizing inorganic oxides through the use of liquid precursors. By drying under different conditions, various types of gels can be formed. Xerogels are dried under ambient conditions where the porous structure of the

wet gel collapses under capillary pressure and a semi-