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Transportation of coumarin 6 nanocrystals with two particle sizes across different biological barriers in embryonic, larval and adult zebrafish.
Li, Y.; Miao, X.; Chen, T.; Yi, X.; Wang, R.; Lee, M. Y.; Wang, X.; Zheng, Y.
2016-08-22
Source Publication2016 Chinese Pharmaceutical Conference
AbstractIn recent decades, the application of nanotechnology for medicine and more specifically for drug delivery systems (DDS) has increased rapidly. Several biological barriers need to be overcome for nanosized DDS after administration, such as blood brain barrier (BBB), gastrointestinal (GI) barrier and blood retinal barrier (BRB) etc. To facilitate rapid development of DDS, an ideal model that is suitable for high-through screening of the novel formulation or excipient across several biological barriers was desperately needed. Zebrafish have emerged as useful vertebrate models for the optical tracking and biocompatibility assessment because of their transparent body and close homology with human. More importantly, there is an increasing amount of evidence showing highly conserved nature of both structure and function of biological barriers when compared with mammals. In this study, a highly fluorescent, lipophilic and poorly absorbable compound named coumarin-6 (C6) was formulated as C6-nanocrystals (C6-NCs) as the model nano DDS with average particle size of 67.5± 5.2 nm and 190±9.2 nm. The permeability of NCs across chorion was examined with embryos first. Two sized C6-NCs entered embryos across the chorion and were mainly deposited in the yolk sac, where 70 nm NCs accumulated more than 200 nm NCs in both yolk sac and the inner mass of embryos but no fluorescence could be observed in C6 suspension group, indicating that chorion showed higher permeability to small sized NCs. Transportation across BBB, BRB and GI barrier were visualized and indicated by fluorescence with zebrafish larvae. Strong fluorescence was observed in the C6-NCs treated groups. In comparison with 200 nm C6-NCs treated group, high fluorescence intensity was observed for 70 nm C6-NCs by zebrafish, indicating the higher uptake efficiency. This result further supported that particles size of NCs plays an important role in drug delivery efficiency. Moreover, C6-NCs were successfully transported to the whole body of zebrafish where high fluorescent was found to be accumulated in the intestine, eye, gall bladder and brain, revealing that C6 was partly absorbed by oral route and afterwards it could transport across the BBB, BRB and GI barrier. These findings suggest that nanosized DDS could enhance permeability of poorly absorbed drug across biological barriers in vivo. Zebrafish could be developed as a useful in vivo predictive model to study transport of nanosized drug delivery system across the biological barriers.
KeywordTransportation particle sizes biological barriers zebrafish
Language英語English
The Source to ArticlePB_Publication
PUB ID33431
Document TypeConference paper
CollectionDEPARTMENT OF PHARMACEUTICAL SCIENCES
Corresponding AuthorZheng, Y.
Recommended Citation
GB/T 7714
Li, Y.,Miao, X.,Chen, T.,et al. Transportation of coumarin 6 nanocrystals with two particle sizes across different biological barriers in embryonic, larval and adult zebrafish.[C], 2016.
APA Li, Y.., Miao, X.., Chen, T.., Yi, X.., Wang, R.., Lee, M. Y.., Wang, X.., & Zheng, Y. (2016). Transportation of coumarin 6 nanocrystals with two particle sizes across different biological barriers in embryonic, larval and adult zebrafish.. 2016 Chinese Pharmaceutical Conference.
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