کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2484784 1114337 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mechanistic Study of the Uptake/Permeation of Cell-Penetrating Peptides Across a Caco-2 Monolayer and Their Stimulatory Effect on Epithelial Insulin Transport
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Mechanistic Study of the Uptake/Permeation of Cell-Penetrating Peptides Across a Caco-2 Monolayer and Their Stimulatory Effect on Epithelial Insulin Transport
چکیده انگلیسی
Our recent studies have demonstrated the potential of cell-penetrating peptides (CPPs) to significantly stimulate the intestinal absorption of therapeutic peptides and proteins. This study examined the mechanisms underlying the intestinal epithelial uptake and permeation of CPPs and their contribution to the enhanced absorption of insulin. Fluorescein-tagged octaarginine (R8) and penetratin were used as the promising CPPs, and in vitro uptake and permeation assays were conducted using Caco-2 cell monolayer. The assay conducted under low temperature conditions revealed that energy-dependent pathways are not involved in d-form arginines (d-R8) uptake or its stimulatory effect on insulin uptake. The Km value (3.82 μM), calculated from the dose dependence of d-R8 uptake, suggested that a part of the d-R8 uptake was saturated at the functional concentration (60 μM d-R8). An analysis based on the binding parameters of insulin and d-R8 also showed an increase in the uptake clearance of the insulin/d-R8 complex, even at a saturated concentration of d-R8, implying that this complex is taken up by Caco-2 cells via pathways that differ from those that take up unbound d-R8. Thus, this study suggests that CPPs such as oligoarginines stimulate the intestinal epithelial transport of peptide and protein drugs via energy-independent unsaturable internalization.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 11, November 2013, Pages 3998-4008
نویسندگان
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