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Zebrafish as a visual and dynamic model to study the transport of nanosized drug delivery systems across the biological barriers
Li Y.3; Miao X.3; Chen T.3; Yi X.1; Wang R.3; Zhao H.4; Lee S.M.-Y.3; Wang X.2; Zheng Y.3
Source PublicationColloids and Surfaces B: Biointerfaces
ISSN18734367 09277765

With the wide application of nanotechnology to drug delivery systems, a simple, dynamic and visual in vivo model for high-throughput screening of novel formulations with fluorescence markers across biological barriers is desperately needed. In vitro cell culture models have been widely used, although they are far from a complimentary in vivo system. Mammalian animal models are common predictive models to study transport, but they are costly and time consuming. Zebrafish (Danio rerio), a small vertebrate model, have the potential to be developed as an “intermediate” model for quick evaluations. Based on our previously established coumarin 6 nanocrystals (C6-NCs), which have two different sizes, the present study investigates the transportation of C6-NCs across four biological barriers, including the chorion, blood brain barrier (BBB), blood retinal barrier (BRB) and gastrointestinal (GI) barrier, using zebrafish embryos and larvae as in vivo models. The biodistribution and elimination of C6 from different organs were quantified in adult zebrafish. The results showed that compared to 200 nm C6-NCs, 70 nm C6-NCs showed better permeability across these biological barriers. A FRET study suggested that intact C6-NCs together with the free dissolved form of C6 were absorbed into the larval zebrafish. More C6 was accumulated in different organs after incubation with small sized NCs via lipid raft-mediated endocytosis in adult zebrafish, which is consistent with the findings from in vitro cell monolayers and the zebrafish larvae model. C6-NCs could be gradually eliminated in each organ over time. This study demonstrated the successful application of zebrafish as a simple and dynamic model to simultaneously assess the transport of nanosized drug delivery systems across several biological barriers and biodistribution in different organs, especially in the brain, which could be used for central nervous system (CNS) drug and delivery system screening.

KeywordBiological Barriers Nanocrystals Transport Zebrafish
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Indexed BySCI
WOS Research AreaBiophysics ; Chemistry ; Materials Science
WOS SubjectBiophysics ; Chemistry, Physical ; Materials Science, bioMaterials
WOS IDWOS:000405041500026
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Cited Times [WOS]:23   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27516, United States
2.Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
3.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
4.Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, Chi
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Li Y.,Miao X.,Chen T.,et al. Zebrafish as a visual and dynamic model to study the transport of nanosized drug delivery systems across the biological barriers[J]. Colloids and Surfaces B: Biointerfaces,2017,156:227-235.
APA Li Y..,Miao X..,Chen T..,Yi X..,Wang R..,...&Zheng Y..(2017).Zebrafish as a visual and dynamic model to study the transport of nanosized drug delivery systems across the biological barriers.Colloids and Surfaces B: Biointerfaces,156,227-235.
MLA Li Y.,et al."Zebrafish as a visual and dynamic model to study the transport of nanosized drug delivery systems across the biological barriers".Colloids and Surfaces B: Biointerfaces 156(2017):227-235.
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