کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487134 | 1114405 | 2009 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification of Tight Junction Modulating Lipids
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کلمات کلیدی
Alkylglycosides - آلکیل گلیکوزیدهاTight junction - اتصال تنگepithelial delivery/permeability - تحویل / نفوذ پذیری اپیتلیالMucosal delivery - تحویل مخاطیNasal absorption - جذب بینیceramides - سرامیدOxidized lipid - لیپید اکسید شدهEther lipids - لیپید های اترLipids/lipoproteins - لیپیدها / لیپوپروتئین ها
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Tight junctions (TJs) play an important role in regulating paracellular drug transport. The aim of this study was to identify lipids that rapidly and reversibly alter transepithelial electrical resistance (TER) and/or TJ permeability in epithelial tissue. In this study, we developed a screen for identifying lipids that alter TJ properties. Measurement of TER was used to monitor TJ activity on bronchial/tracheal epithelial tissues using a microtiter format. Among seven groups of lipids tested, four classes were identified as TJ modulators (sphingosines, alkylglycosides, oxidized lipids and ether lipids). Individual lipids within these four classes showed up to 95% TER reduction at noncytotoxic concentrations. Alkylglycosides, however, showed high cytotoxicity and low viability at concentrations (0.2-0.4%) reported to enhance transmucosal absorption (Ahsan et al., 2003, Int J Pham 251: 195-203). Several active lipids also showed enhanced permeation of FITCâlabeled dextran (m.w. 3000). Immunofluorescence staining of PGPCâtreated cells with antibodies against ZOâ1, occludin and claudin 4 showed no detectable changes in TJ structural morphology, indicating that a nondestructive, submicroscopic alteration in TJ function may be involved in TER reduction and permeation enhancement. This study demonstrates that three new classes of lipids, excluding alkylglycosides, show potential utility for transmucosal drug delivery. © 2008 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 98:606-619, 2009
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 98, Issue 2, February 2009, Pages 606-619
Journal: Journal of Pharmaceutical Sciences - Volume 98, Issue 2, February 2009, Pages 606-619
نویسندگان
ShuâChih ChenâQuay, Kristine T. Eiting, Angela W.âA. Li, Najib Lamharzi, Steven C. Quay,