کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6857 522 2013 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Transferrin receptor specific nanocarriers conjugated with functional 7peptide for oral drug delivery
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Transferrin receptor specific nanocarriers conjugated with functional 7peptide for oral drug delivery
چکیده انگلیسی

In an attempt to increase the interaction of a nanocarrier system with gastrointestinal epithelial cells, a transferrin receptor (TfR) specific 7peptide was conjugated to PEG-b-PCL copolymer and the functional nanocarriers were constructed and characterized. The endocytosis, intracellular trafficking and transcytosis of such nanocarriers loaded with coumarin 6 (7pep-M-C6) in a human colon carcinoma cell line (Caco-2) were investigated, followed by the in vivo intestine distribution study. The real-time imaging of live cell, three dimensional reconstruction of confocal image, quantitative colocalization analysis and other techniques were applied. First, the TfR expression was confirmed in Caco-2. Then, 7pep-M-C6 exhibited higher intracellular uptake compared with unmodified nanocarriers. In a live cell study, 7pep-M-C6 demonstrated faster uptake kinetics especially in the surface of cells. Together with a competition study using TfR antibody, it was proved that the increased cellular uptake was due to a receptor-mediated mechanism. Besides the unspecific endocytosis pathway, 7pep-M-C6 was found to enter the cells through a specific clathrin-mediated mechanism, related to the expression of TfR on Caco-2 cells. Possibly for this reason, 7pep-M-C6 tended to colocalize more with late endosomes and lysosomes than the control micelles. Also for the same mechanism, the increased transport of 7pep-M-C6 across Caco-2 monolayer was found, through a transcellular but not a paracellular pathway, while an increased in vivo intestinal distribution of 7pep-M-C6 was observed. In conclusion, the functional nanocarriers could specifically interact with gastrointestinal endothelial cells, increase their transport and alter their pathway as a result.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 34, Issue 3, January 2013, Pages 794–806
نویسندگان
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