کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2485248 1114350 2012 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Improved Transnasal Transport and Brain Uptake of Tizanidine HCl-Loaded Thiolated Chitosan Nanoparticles for Alleviation of Pain
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Improved Transnasal Transport and Brain Uptake of Tizanidine HCl-Loaded Thiolated Chitosan Nanoparticles for Alleviation of Pain
چکیده انگلیسی
The aim of this study was to prepare and characterize thiolated chitosan (TC) nanoparticles (NPs) of tizanidine HCl (TZ) and to evaluate its transport across monolayer of RPMI 2650 cells (Human nasal septum carcinoma cell line) followed by assessment of their pharmacokinetic and pharmacodynamic attributes, after intranasal (i.n.) administration. Chitosan was thiolated by carbodiimide method and thiolation was confirmed qualitatively and quantitatively. NPs were prepared using ionotropic gelation and evaluated for mucoadhesion using sheep nasal mucosa for drug permeation and cytotoxicity using monolayer of RPMI 2650 cells. Drug biodistribution was evaluated after technetium-99m labeling, visualized using gamma camera, and evaluated pharmacodynamically by measuring antinociceptive activity in mice. High mucoadhesion and permeation of drug were observed for TC NPs with least toxicity to nasal epithelial cells. Brain uptake and antinociceptive effect of the drug were significantly enhanced after thiolation of chitosan. This concludes that TC NPs, after i.n. administration, show significant increase in the mucoadhesion, reduction in cytotoxicity, enhanced permeation across cells monolayer, higher TZ brain uptake, and considerable increase in antinociceptive activity of TZ in mice. These features make TC an interesting polymer for demonstrating appreciable improvement of transnasal permeation of hydrophilic drugs, such as TZ, known to have limited permeation across blood-brain barrier. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 2, February 2012, Pages 690-706
نویسندگان
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