| Status | 已發表Published |
| Zebrafish: a model to evaluate biofate of transferrin receptor-targeted 7peptide-decrated coumarin 6 micelles | |
Li, Y. ; Song, X.; Yi, X.; Wang, R. ; Lee, M. Y.; Wang, X.; Zheng, Y.
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| 2017-11-13 | |
| Source Publication | 2017 AAPS Annual Meeting Exposition
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| Abstract | Purpose Understanding of the dynamic process that happens after in vivo delivery of targeted nanoparticles is very important. In this study, we have developed and validated zebrafish as an in vivo visible model to evaluate the biofate of transferrin receptor (TfR)-targeted 7peptide (7pep)-decorated coumarin 6 (C6) micelles. Methods TfR expression in different development stages and tissues of zebrafish was validated by the whole mount immunostaining. 7pep decorated micelles loaded with C6 (7pep-M-C6) with different ligand density were prepared by an anti-solvent precipitation method and micelles without 7pep modification (M-C6) were used as the control. The delivery efficacy of these delivery systems in the retina, brain and intestine were compared using ultra-microtome and confocal imaging. The in vivo integrity of the functional micelles for oral delivery was explored in adult zebrafish using FRET technology. Results The expression level of TfR in the retina, brain and intestine were demonstrated increasing along with the development time (Fig. 1). The particle size of 7pep-M-C6 with different ligand density was between 30-40 nm. Compared to M-C6, 7pep-M-C6 demonstrated higher uptake efficiency in the larval zebrafish with endocytosis pathway participation. Confocal images of larval zebrafish eye and brain showed efficient delivery of C6 across the retinal pigment epithelial to the ganglion cell layer and significant accumulation of C6 all over the brain tissues, respectively, which reached to a plateau when the ligand density was 10% (Fig. 2). After oral administration ,7pep-M-C6 enhanced transport of C6 across the villi and aggregated in the basolateral membrane of the intestine of adult zebrafish. Moreover, C6 could accumulated in the eye and brain. FRET analysis suggested that intact 7pep modified micelles (10%) could enter the epithelial cells of intestine after oral administration in adult zebrafish. Conclusion This study provides strong evidence that zebrafish could be used as an easy and visible model for in vivo biofate assessment of TfR-targeted drug delivery systems. |
| Keyword | Zebrafish transferrin receptor |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 40859 |
| Document Type | Conference paper |
| Collection | DEPARTMENT OF PHARMACEUTICAL SCIENCES |
| Corresponding Author | Zheng, Y. |
| Recommended Citation GB/T 7714 | Li, Y.,Song, X.,Yi, X.,et al. Zebrafish: a model to evaluate biofate of transferrin receptor-targeted 7peptide-decrated coumarin 6 micelles[C], 2017. |
| APA | Li, Y.., Song, X.., Yi, X.., Wang, R.., Lee, M. Y.., Wang, X.., & Zheng, Y. (2017). Zebrafish: a model to evaluate biofate of transferrin receptor-targeted 7peptide-decrated coumarin 6 micelles. 2017 AAPS Annual Meeting Exposition. |
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