کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9918940 | 1557563 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Vitamin C and 6-amino-vitamin C conjugates of diclofenac: synthesis and evaluation
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
علوم دارویی
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![عکس صفحه اول مقاله: Vitamin C and 6-amino-vitamin C conjugates of diclofenac: synthesis and evaluation Vitamin C and 6-amino-vitamin C conjugates of diclofenac: synthesis and evaluation](/preview/png/9918940.png)
چکیده انگلیسی
Diclofenac (Diclo), its ascorbic acid (AA) or 6-amino-AA (AA-NH2) pro-drugs (AA-Diclo or AA-NH-Diclo) were prepared and evaluated on human retinal pigment epithelium (HRPE) cells to investigate their ability to interact with the vitamin C transporter SVCT2 and their cellular uptake. Furthermore, stabilities in physiological fluids of these compounds were investigated. For kinetic experiments, AA-Diclo was incubated in Tris-HCl buffer, human plasma or whole blood. The extracted samples were analysed by HPLC. AA-Diclo was hydrolysed following first order kinetics in buffer, plasma (t1/2 about 10Â h) and whole blood (t1/2 about 3.5Â h). Transport and inhibition assays were performed by adding [14C]AA and the above-mentioned unlabelled compounds to plated HRPE cells. Intracellular accumulation was measured incubating HRPE cells with increasing concentrations of unlabelled compounds, following by HPLC analysis. Diclo resulted as a non-competitive inhibitor of AA-transport, showing a Na+-dependent and ascorbate-independent uptake. AA-Diclo behaved as a competitive inhibitor, but it was not transported into cells, whereas its analogue AA-NH-Diclo showed a decreased inhibitory activity. Stability studies suggest AA-Diclo as a potential candidate to enhance the Diclo short half life in vivo. The discovery of a Na+-dependent transporter for Diclo on HRPE cells opens new perspectives for targeting diclofenac into the brain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 291, Issues 1â2, 3 March 2005, Pages 171-181
Journal: International Journal of Pharmaceutics - Volume 291, Issues 1â2, 3 March 2005, Pages 171-181
نویسندگان
A. Dalpiaz, B. Pavan, M. Scaglianti, F. Vitali, F. Bortolotti, C. Biondi, A. Scatturin, S. Manfredini,