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Transmembrane Pathways and Mechanisms of Rod-like Paclitaxel Nanocrystals through MDCK Polarized Monolayer
Deng, Feiyang1; Zhang, Hua1; Wang, Xing1; Zhang, Yuan3; Hu, Hongxiang1; Song, Siyang1; Dai, Wenbing1; He, Bing1; Zheng, Ying4; Wang, Xueqing1; Zhang, Qiang1,2
2017-02-22
Source PublicationACS APPLIED MATERIALS & INTERFACES
ISSN1944-8244
Volume9Issue:7Pages:5803-5816
Abstract

Drug nanocrystals (NCs) appear to be favorable to improving oral bioavailability of poorly water-soluble drugs as evidenced by the great success they have had in the market. However, the pathway and mechanism of drug NCs through epithelial membrane are still unclear. In an attempt to clarify their transport features, paclitaxel nanocrystals (PTX-NCs), and paclitaxel hybrid NCs with lipophilic carbocyanine dyes, were prepared and characterized as the models. The endocytosis, intracellular trafficking, paracellular transport, and transcytosis of PTX-NCs were carefully investigated with Forster resonance energy transfer (FRET) analysis, as well as a colocalization assay, flow cytometry, gene silencing, Western-blot, transepithelial electrical resistance (TEER) study and other approaches on MDCK cells. It was found that rod-like PTX-NCs could transport through the monolayer intact, and the process of endocytosis proved to be time and energy dependent. Endoplasmic reticulum (ER) and Golgi complexes were colocalized with PTX-NCs in cells, so the ER Golgi complexes/Golgi complexes basolateral membrane pathway may be involved in,the intracellular trafficking and transcytosis of PTX-NCs. It was demonstrated here that cav-1, dynamin, and actin filament modulated the endocytosis process, and Cdc 42 regulated the transcytosis process. In addition, no paracellular transport of PTX-NCs was observed. These findings demonstrated that the rod-like nanocrystals not only enhanced the transcytosis of PTX compared with micropartides of raw drug materials but also changed the pathways of drug delivery. This study certainly provides insight for the oral absorption mechanism of nanocrystals of poorly soluble drugs.

KeywordNanocrystals Mdck Monolayer Endocytosis Intracellular Transport Transcytosis
DOIhttps://doi.org/10.1021/acsami.6b15151
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics ; Materials Science
WOS SubjectNanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS IDWOS:000394829800017
PublisherAMER CHEMICAL SOC
The Source to ArticleWOS
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被引频次[WOS]:10   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题Institute of Chinese Medical Sciences
Corresponding AuthorWang, Xueqing
Affiliation1.Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
2.The State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China
3.Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island 02881, United States
4.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
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Deng, Feiyang,Zhang, Hua,Wang, Xing,et al. Transmembrane Pathways and Mechanisms of Rod-like Paclitaxel Nanocrystals through MDCK Polarized Monolayer[J]. ACS APPLIED MATERIALS & INTERFACES,2017,9(7):5803-5816.
APA Deng, Feiyang.,Zhang, Hua.,Wang, Xing.,Zhang, Yuan.,Hu, Hongxiang.,...&Zhang, Qiang.(2017).Transmembrane Pathways and Mechanisms of Rod-like Paclitaxel Nanocrystals through MDCK Polarized Monolayer.ACS APPLIED MATERIALS & INTERFACES,9(7),5803-5816.
MLA Deng, Feiyang,et al."Transmembrane Pathways and Mechanisms of Rod-like Paclitaxel Nanocrystals through MDCK Polarized Monolayer".ACS APPLIED MATERIALS & INTERFACES 9.7(2017):5803-5816.
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