In Vivo Evaluation of 5-Fluorouracil-Containing Self-Expandable Nitinol Stent in Rabbits: Efficiency in Long-Term Local Drug Delivery Sheng-Rong Guo,

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In Vivo Evaluation of 5-Fluorouracil-Containing Self-Expandable Nitinol Stent in Rabbits: Efficiency in Long-Term Local Drug Delivery Sheng-Rong Guo, Zhong-Min Wang, Ya-Qiong Zhang, Lei Lei, Jing-Min Shi, Ke-Min Chen, Zhang Yu Journal of Pharmaceutical Sciences Volume 99, Issue 7, Pages 3009-3018 (July 2010) DOI: 10.1002/jps.22066 Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 1 Schematic of the 5-FU-loaded stent. Journal of Pharmaceutical Sciences 2010 99, 3009-3018DOI: (10.1002/jps.22066) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 2 In vitro profiles of cumulative 5-FU. Each point together with error bar represents the mean±SD (n=6). (a) Diffused from the coating of Stent III (■, directly from the drug-loaded layer; ●, through the protective layer); (b) released from coatings of various stents (■, Stent III; ●, Stent II; ▲, Stent I). Journal of Pharmaceutical Sciences 2010 99, 3009-3018DOI: (10.1002/jps.22066) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 3 Radiograph of 5-FU-loaded stent in rabbit (a, stent mounted in introducer and inset; b, fully expanded stent; arrow=stent). Journal of Pharmaceutical Sciences 2010 99, 3009-3018DOI: (10.1002/jps.22066) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 4 Profiles of serum 5-FU concentration versus time for various stents. Each point together with error bar represents the mean±SD (n=5-7). (▲, Stent III; ●, Stent II; ■, Stent I; the serum concentrations below LLOQ are taken as zero). Journal of Pharmaceutical Sciences 2010 99, 3009-3018DOI: (10.1002/jps.22066) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 5 Concentrations of 5-FU in stent-touching esophageal tissue at various time points. Note: (b) is a locally zoomed in view of (a); each bar represents the mean±SD (n=4-6). Journal of Pharmaceutical Sciences 2010 99, 3009-3018DOI: (10.1002/jps.22066) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 6 Concentrations of 5-FU in stent-touching esophageal tissue, liver, and serum for Stent III at various time points. Note: the bars of serum comply with the right scale; each bar represents the mean±SD (n=4–6). Journal of Pharmaceutical Sciences 2010 99, 3009-3018DOI: (10.1002/jps.22066) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 7 Schematic of various investigated segments of rabbit esophagus. Journal of Pharmaceutical Sciences 2010 99, 3009-3018DOI: (10.1002/jps.22066) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 8 5-FU concentrations in mucosa layers and muscle layers of various esophageal segments after implantation with Stent III. Each bar represents the mean±SD (n=4–6). Journal of Pharmaceutical Sciences 2010 99, 3009-3018DOI: (10.1002/jps.22066) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 9 SEM images of stent-touching and adjacent esophageal mucosae of rabbits at 2days after implantation with Stent I and III (scale bar is 10mm; a, the control normal mucosa; b and d, the stent-touching mucosa for Stent I and III, respectively; c and e, the adjacent mucosa for Stent I and III, respectively). Journal of Pharmaceutical Sciences 2010 99, 3009-3018DOI: (10.1002/jps.22066) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions