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[摘要]：Fluorescence diagnosis following oral administration of 5-aminolevulinic acid (5-ALA) has shown to enable the sensitive visualization of intestinal metaplasia, dysplasia and early carcinoma in Barrett's esophagus. Once being established, this technique will be a potential alternative to today's standard diagnosis, i.e. four-quadrant random biopsies which are taken every 1-2 cm of the esophagus for histopathological analysis. In order to further improve this methodology, topical application of lipophilic 5-ALA esters to the esophagus could be advantageous in terms of fluorescence contrast and fluorescence intensity in the target tissue, adverse side effects, as well as application time. Therefore, the aim of this study was to develop a bioadhesive formulation loaded with hexylaminolevulinate (HAL) targeting the esophageal lining. In the present study, different mucoadhesive gels including poloxamer 407, cross-linked polyacrylic acid, hydroxypropylmethylcellulose, sodium carboxymethylcellulose and chitosan have been evaluated with respect to bioadhesion to the esophagus using an ex vivo rat model and a clinical study on healthy volunteers. In order to visualize the mucoadhesive proper-ties of the formulations, a blue dye was incorporated as contrast agent. Chitosan has shown the best esophageal adhesion both in vitro and in vivo. Furthermore, using the in vitro release profiles from chitosan loaded with 40 mM of HAL, one can estimate that after a residence time of 10 min on the esophageal wall, the amount of HAL delivered to the epithelium will be sufficient to perform fluorescence diagnosis of Barrett's esophagus following swallowing of this formulation. (c) 2007 Elsevier B.V. All rights reserved. |
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