کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5818322 1557325 2015 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Goblet cell targeting nanoparticle containing drug-loaded micelle cores for oral delivery of insulin
ترجمه فارسی عنوان
هدف قرار دادن سلولهای گلبول قرمز حاوی هسته میسلهای حاوی مواد دارویی برای تحویل دهان انسولین
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
چکیده انگلیسی

Oral administration of insulin remains a challenge due to its poor enzymatic stability and inefficient permeation across epithelium. We herein developed a novel self-assembled polyelectrolyte complex nanoparticles by coating insulin-loaded dodecylamine-graft-γ-polyglutamic acid micelles with trimethyl chitosan (TMC). The TMC material was also conjugated with a goblet cell-targeting peptide to enhance the affinity of nanoparticles with epithelium. The developed nanoparticle possessed significantly enhanced colloid stability, drug protection ability and ameliorated drug release profile compared with graft copolymer micelles or ionic crosslinked TMC nanoparticles. For in vitro evaluation, Caco-2/HT29-MTX-E12 cell co-cultures, which composed of not only enterocyte-like cells but also mucus-secreting cells and secreted mucus layer, were applied to mimic the epithelium. Intracellular uptake and transcellular permeation of encapsulated drug were greatly enhanced for NPs as compared with free insulin or micelles. Goblet cell-targeting modification further increased the affinity of NPs with epithelium with changed cellular internalization mechanism. The influence of mucus on the cell uptake was also investigated. Ex vivo performed with rat mucosal tissue demonstrated that the nanoparticle could facilitate the permeation of encapsulated insulin across the intestinal epithelium. In vivo study preformed on diabetic rats showed that the orally administered nanoparticles elicited a prolonged hypoglycemic response with relative bioavailability of 7.05%.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 496, Issue 2, 30 December 2015, Pages 993-1005
نویسندگان
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