An Efficient Drug Metabolism Strategy Based on Microsome-Mesoporous Organosilica Nanoreactors
A rapid and accurate in-vitro drug metabolism strategy has been proposed based on the design of a biomimetic nanoreactor composed of amino-functionalized periodic mesoporous organosilica (NH2-PMO) and microsomes. The amphiphilic and positive charged NH2-PMO makes it highly suited for the immobilization of hydrophobic and negatively charged microsomes to form nanoreactors, which can in turn extract substrates from solutions. Such nanoreactors provide a suitable environment to confine multiple enzymes and substrates with high local concentrations, as well as to maintain their catalytic activities for rapid and highly effective drug metabolic reactions. Coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis, the metabolites of nifedipine and testosterone were characterized and the reaction kinetics was quantitatively evaluated. Both the metabolism conversion and reaction rate were significantly improved with the NH2-PMO nanoreactors compared to bulk reactions. This strategy is simple and cost-effective for promising advances in biomimetic metabolism study.