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The effect of ph and ligand density on the endocytosis and exocytosis process of fcbp decorated PEG-PCL micelles on Caco-2 cells
Song X.-N.1; Li R.1; Zhang H.1; Dai W.-B.1; He B.1; Zheng Y.2; Zhang Q.1; Wang X.-Q.1
2017
Source PublicationYaoxue Xuebao
ISSN05134870
Volume52Issue:8Pages:1331-1336
AbstractThe difference in pH between apical and basolateral side of intestinal epithelial and pH dependence character of the combination of FcRn (neonatal Fc receptor) and ligand might improve the delivery of hydrophobic drugs by facilitating the transcytosis of nanocarriers. Here we designed FcBP (IgG Fc domain-binding peptides) decorated coumarin 6 (C6) loaded poly(ethyl ethylene phosphate)-co-poly(e-caprolactone) (PEG-PCL) micelles with different ligand densities to study the effect of pH and ligand density on the endocytosis and exocytosis process of micelles on human colon adenanocaricinoma cell lines (Caco-2). Active micelles with different ligand densities and passive micelles were prepared using the thin-film hydration method. The size of the micelles was characterized by dynamic light scattering analysis and the morphology was observed by transmission electron microscope. The endocytosis and exocytosis of the micelles at pH 7.4 and pH 6.0, as well as the effect of FcRn on the endocytosis, were investigated by flow cytometry. The results showed that the size of micelles was about 30 nm, which was not affected by FcBP decoration. We found that pH and ligand density could both influence the endocytosis. The uptake of active micelles was higher at pH 6.0 than at pH 7.4, and an optimal ligand density of endocytosis was appeared in both pH environment. Then we proved that FcBP decorated micelles could be endocytosed at pH 6.0 and exocytosed at pH 7.4, and the exocytosis process was also related to ligand density. Micelles with 10% ligand density had the largest exocytosis, showing the potentiality to deliver drugs through the intestinal epithelial. In addition, the competitive inhibition experiments illustrated that the interaction between FcRn and FcBP were essential to endocytosis. The results will enhance the understanding on the FcBP decorated PEG-PCL micelles for transmemberane drug delivery.
KeywordEndocytosis and exocytosis IgG Fc domain-binding peptide Ligand density Micelle Neonatal Fc receptor PH
DOI10.16438/j.0513-4870.2017-0358
URLView the original
Language英語
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Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Peking University
2.Universidade de Macau
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GB/T 7714
Song X.-N.,Li R.,Zhang H.,et al. The effect of ph and ligand density on the endocytosis and exocytosis process of fcbp decorated PEG-PCL micelles on Caco-2 cells[J]. Yaoxue Xuebao,2017,52(8):1331-1336.
APA Song X.-N..,Li R..,Zhang H..,Dai W.-B..,He B..,...&Wang X.-Q..(2017).The effect of ph and ligand density on the endocytosis and exocytosis process of fcbp decorated PEG-PCL micelles on Caco-2 cells.Yaoxue Xuebao,52(8),1331-1336.
MLA Song X.-N.,et al."The effect of ph and ligand density on the endocytosis and exocytosis process of fcbp decorated PEG-PCL micelles on Caco-2 cells".Yaoxue Xuebao 52.8(2017):1331-1336.
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