کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5550941 1557304 2016 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Direct in vivo evidence on the mechanism by which nanoparticles facilitate the absorption of a water insoluble, P-gp substrate
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
پیش نمایش صفحه اول مقاله
Direct in vivo evidence on the mechanism by which nanoparticles facilitate the absorption of a water insoluble, P-gp substrate
چکیده انگلیسی

Here we examine the mechanisms by which nanoparticles enable the oral absorption of water-insoluble, P-glycoprotein efflux pump (P-gp) substrates, without recourse to P-gp inhibitors. Both 200 nm paclitaxel N-(2-phenoxyacetyl)-6-O-glycolchitosan (GCPh) nanoparticles (GCPh-PTX) and a simulated Taxol formulation, facilitate drug dissolution in biorelevant media, unlike paclitaxel nanocrystals. Verapamil (40 mg kg−1) increased the oral absorption from low dose Taxol (6 or 10 mg kg−1) by 100%, whereas the oral absorption from high dose Taxol (20 mg kg−1) or low dose GCPh-PTX (6 or 10 mg kg−1) was largely unchanged by verapamil. There was virtually no absorption from control paclitaxel nanocrystals (20 mg kg−1). Imaging of ex-vivo rat ileum samples showed that fluorescently labelled GCPh nanoparticles are mucoadhesive and are taken up by ileum epithelial cells. GCPh nanoparticles were also found to open Caco-2 cell tight junctions. In conclusion, mucoadhesive, drug solubilising GCPh nanoparticles enable the oral absorption of paclitaxel via the saturation of the P-gp pump (by high local drug concentrations) and by particle uptake and tight junction opening mechanisms.

Rat ileum showing orally dosed particles (red) in the villi and basement membrane (yellow arrows) and adhering to the mucus (white arrows).133

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 514, Issue 1, 30 November 2016, Pages 121-132
نویسندگان
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