Caco-2 cell monolayers as a tool to study simultaneous phase II metabolism and metabolite efflux of indomethacin, paracetamol and 1-naphthol.

The human intestinal cell line, Caco-2, was used to study compounds - indomethacin, paracetamol and 1-naphthol - that undergo intestinal phase II metabolism followed by apical and/or basolateral efflux of the metabolites and/or parent compounds. The interplay was studied during permeability experiments across fully differentiated Caco-2 cell monolayers. The parent compounds and their glucuronide and/or sulfate metabolites were detected by LC-MS/MS. Conjugation of the model compounds and effluxes of their metabolites were observed. The efflux of indomethacin glucuronide was apical, but complementary basolateral efflux was observed at the highest indomethacin concentration (500 microM), probably due to apical saturation. Paracetamol glucuronide was not formed in these experiments, but apical and basolateral effluxes of paracetamol sulfate were observed. A typical bell-shaped inhibition curve was observed for the formation of 1-naphthol glucuronides, indicating substrate or product inhibition of the UGT enzyme(s) at higher 1-naphthol concentrations (200 microM and 500 microM). Based on these results, the fully differentiated Caco-2 cell monolayers can be applied as a platform for qualitative in vitro studies, where phase II metabolism and efflux activities are ongoing simultaneously.

Mesoporous silicon in drug delivery applications.

During the last few years, a number of interesting drug delivery applications of mesoporous materials have been demonstrated. Mesoporous silicon has many important properties advantageous to drug delivery applications. The small size of the pores confines the space of a drug and engages the effects of surface interactions of the drug molecules and the pore wall. The size of the pores and the surface chemistry of the pore walls may be easily changed and controlled. Depending on the size and the surface chemistry of the pores, increased or sustained release of the loaded drug can be obtained. Drug loading from a solution at room temperature enables the use of porous silicon (PSi) also with sensitive therapeutic compounds susceptible to degradation, like peptides and proteins. This article reviews the fabrication and chemical modifications of PSi for biomedical applications, and also the potential advantages of PSi in drug delivery.