title: Efficient drug metabolism strategy based on microsome-mesoporous organosilica nanoreactors.
abstract: 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 nature and positive charge of NH2-PMO make 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 analysis, the metabolites of nifedipine and testosterone were quantitatively characterized, and the reaction kinetics was 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.
authors.affiliation: Department of Chemistry, Institutes of Biomedical Sciences, and State Key Laboratory of Molecular Engineering of Polymers, Fudan University , Shanghai 200433, China.
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Fang
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Feng
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Zhang
authors.forename: Hubert H
authors.initials: HH
authors.lastname: Girault
authors.forename: Baohong
authors.initials: B
authors.lastname: Liu
mesh_terms: D032701:Biomimetics; D002851:Chromatography, High Pressure Liquid; D057927:Hydrophobic and Hydrophilic Interactions; D013058:Mass Spectrometry; D046529:Microscopy, Electron, Transmission; D008861:Microsomes / Q000378:metabolism*; D036103:Nanotechnology; D009543:Nifedipine / Q000493:pharmacokinetics*; D013739:Testosterone / Q000493:pharmacokinetics*
chemical_list: D013739:Testosterone; D009543:Nifedipine