Cellular Uptake and Metabolism of Soluplus-based Scopoletin Micelles in Caco-2 Cells
ZENG Ying-chun1,2, JI Zhong-hua3, XIE Xing-liang2, ZHANG Quan2, ZHENG Ya-xin2*
1. Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College, Chengdu 610500, China; 2. Department of Pharmacy, Chengdu Medical College, Chengdu 610500, China; 3. Department of Pharmaceutical Engineering, Zhejiang Pharmaceutical College, Hangzhou 315100, China
Abstract��OBJECTIVE To develop an analytical method for the quantification of scopoletin (Sco) and investigate the cellular uptake and metabolism of polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol (soluplus)-based Sco micelles (Sco-Ms) in Caco-2 cells, as well as exploring the possible mechanisms involved in the oral absorption of Sco-Ms.METHODS Combined with enzymatic hydrolysis for pretreatment, a liquid chromatography-electrospray ionization-tandem mass spectrometric (LC-MS/MS) method was developed for the quantification of Sco and its corresponding metabolite. Then, cellular uptake efficiency and metabolic rate of Sco were calculated.RESULTS This method was proven to be linear over the concentration range of 5-1 000 ng��mL-1. Cellular uptake of Sco-Ms increased significantly compared with that of free Sco at various time points. Meanwhile, Sco-Ms inhibited the enzymatic degradation of Sco. Sco-Ms were primarily internalized into enterocytes via macropinocytosis and clathrin-dependent pathways.CONCLUSION Enhanced cellular uptake and decreased metabolic rate are pivotal mechanisms by which Sco-Ms promotes oral absorption of Sco.
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2018, Vol. 53 
