title: Transport Mechanism of Coumarin 6 Nanocrystals with Two Particle Sizes in MDCKII Monolayer and Larval Zebrafish.
abstract: Nanocrystals (NCs) were utilized as oral formulations in commercial products to deliver lipophilic drug, but their transport mechanisms are not fully understood. This study aimed to explore the transport mechanism of NCs using in vitro Madin-Darby canine kidney II (MDCK II) cells and in vivo larval zebrafish models. Coumarin 6 (C6) was formulated into NCs with particle size of 67.5 ± 5.2 and 190 ± 9.2 nm. In vitro studies showed that 70 nm NCs accumulated in lysosome and endoplasmic reticulum (ER) as destinations. Lipid raft pathways mediated the endocytosis, while lipid raft, ER/Golgi, and Golgi/plasma membrane pathways were involved in exocytosis and transcytosis process. However, 200 nm NCs accumulated more in a lysosome, where lipid raft pathways were also involved in the endocytosis process. In vivo studies in larval zebrafish model further confirmed that the above network plays an important role in the absorption and distribution of C6-NCs.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Miao
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University , Beijing 100191, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao, China.
authors.forename: Simon Ming-Yuen
authors.initials: SM
authors.lastname: Lee
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D003374:Coumarins / Q000737:chemistry* / Q000378:metabolism; D004285:Dogs; D061985:Madin Darby Canine Kidney Cells; D053758:Nanoparticles / Q000737:chemistry*; D015388:Organelles / Q000378:metabolism; D010316:Particle Size; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism; D015027:Zebrafish
chemical_list: D003374:Coumarins; D013844:Thiazoles; C517282:coumarin 6
keywords: epithelial cells; nanocrystals; particle size; transport mechanism; zebrafish