Microfabricated porous silicon particles enhance paracellular delivery of insulin across intestinal Caco-2 cell monolayers

Purpose. Novel porous silicon microparticles were fabricated and loaded with fluorescein isothiocyanate (FITC)-insulin, a model hydrophilic pharmacologically active protein, along with varied doses of sodium laurate (C12), a well-known permeation enhancer. Methods. Particle and liquid formulations were compared as a function of apical to basolateral flux of FITC-insulin across differentiated human intestinal Caco-2 cell monolayers grown on Transwell(R) inserts. Results. The flux of FITC-insulin from silicon particles across cell monolayers was nearly 10-fold higher compared with liquid formulations with permeation enhancer and approximately 50-fold compared with liquid formulations without enhancer. By increasing C12 dose per particle with a concomitant decrease in total particles added per monolayer, the percent of FITC-insulin transport resulted in a linear increase up to 25% monolayer coverage. Conclusions. Although maintaining monolayer integrity and transepithelial electrical resistance, maximum drug transport (20%/h) was achieved with 0.337 mug C12 dose per particle, and total particle loading at 25% monolayer coverage.