Amphiphilic Mesoporous Foam-Stabilized Pickering Emulsions as Versatile Nanoreactors for In Vitro Drug Metabolism

Abstract

Pickering emulsions have shown great advantages in enzymatic reactions due to their unique properties and functions. Herein, an amphiphilic mesoporous graphene foam-stabilized Pickering emulsion (GFPE) is designed as an CYP450 enzymatic reaction medium to access a highly efficient drug metabolism. Compared with the previous approach, the catalytic activity and stability of multi-enzymes involved in the metabolism can be maintained well, the concentration of the drug and metabolites can be improved significantly, electrons can be transferred from the donors to the CYP heme rapidly, and then the metabolism can be confined in the nanoscale domains to accelerate the metabolic reaction rate. Meanwhile, the proposed GFPE nanoreactor is simple and low-cost in drug metabolism because the metabolites can be extracted directly by the organic phase of the GFPE for downstream liquid chromatography–mass spectrometry analysis as well as effective recycling of the enzyme can be realized. Taking advantage of these attractive features, the first example of a GFPE-based drug metabolism nanoreactor has been successfully applied in the metabolism of real tablets. The metabolism conversion and rate have been significantly improved with the GFPE. The GFPE strategy was further applied to the inhibition assay, where the activity of CYP2C9 involved in the catalysis of tolbutamide can be inhibited by sulfaphenazole effectively. These results suggest that the GFPE can serve as a clinically relevant biotechnological protocol for the rapid development of drugs.