کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2502555 1557386 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nimodipine nanocrystals for oral bioavailability improvement: Role of mesenteric lymph transport in the oral absorption
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
پیش نمایش صفحه اول مقاله
Nimodipine nanocrystals for oral bioavailability improvement: Role of mesenteric lymph transport in the oral absorption
چکیده انگلیسی

PurposeWe had conducted a comprehensive study on preparation, characterization and pharmacokinetics of nimodipine nanocrystals for oral administration previously, and nimodipine nanocrystals displayed lower dissolution profiles but higher bioavailability than Nimotop®. In this study, we aimed at elucidating the reasons of unfavorable in vitro in vivo correlation for NMD nanocrystals and Nimotop® with a hypothesis that special oral absorption mechanism was involved in the absorption of nimodipine nanocrystals.MethodsInvestigations of oral absorption mechanism of the nanocrystals were performed on everted gut sac models, lymphatically (mesenteric lymph duct) cannulated SD rats, Caco-2 cell monolayers and chylomicron flow blocking rats, respectively.ResultsThe permeability of nanocrystals in duodenum, ileum and colon was not superior to that of Nimotop®, suggestive of special absorption mechanisms involved. Exudates of nanocrystals from enterocytes were detected in mesenteric lymphatic fluids using a transmission electron microscope, and the bioavailability was only about half of the control after the mesenteric lymph was blocked. The nanocrystals were taken up by enterocytes via macropinocytosis and caveolin-mediated endocytosis pathways.ConclusionsIt was impossible to establish a favorable in vitro in vivo correlation for NMD nanocrystals and Nimotop®, because portions of the nanocrystals underwent macropinocytosis and caveolin-mediated endocytosis by enterocytes as intact nanocrystal forms, then bypassed the liver first-pass metabolism.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 448, Issue 1, 1 May 2013, Pages 290–297
نویسندگان
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