ADHESIVE MICROSPHERES FOR TREATING BOWEL DISEASES

我们建议开发新的生物粘附微球， 用于胃肠道疾病的口服药物递送系统。 本项目涉及体外生物粘附之间的相关性 通过使用专门的拉伸技术和体内测量的性能 保留时间以及开发所用药物的递送系统 在炎性肠病（IBD），如溃疡性结肠炎（UC）的治疗中， 结肠炎和克罗恩病。需要检验的一个重要假设包括 质子化羧基对生物粘附至关重要的概念，以及 这些可以有效地作用于柔性链， 水凝胶聚合物以及生物可蚀性上更刚性链 热塑性聚合物。为了解决这个问题，我们计划将三个 调查方法。首先，我们将进行直接表面 各种微球的表征以定量微球的量。 羧基或任何其它粘蛋白特异性配体。这些研究报告将 使用ESCA和ATIR。其次，将使用电天平 为了在体外直接测量 聚合物微球和胃肠道的代表性组织，而 保持区域pH环境。三、直接体内评价 粘合剂，不透射线微球，保留超过正常时间 胃肠道运输，将通过系列X射线成像研究， 动物总的来说，这项工作将包括以下阶段：聚合物 从合成和天然存在的聚合物池中选择; 所选材料的合成和表征; 携带硫酸钡、5-氨基水杨酸或 其组合;体外生物粘附研究;生物粘附研究 体内：和体内递送系统效率测试。

We propose to develop novel bioadhesive microspheres which will serve as oral drug delivery systems for diseases of the gastrointestinal tract. This project involves the correlation between in vitro bioadhesion properties measured by using specialized tensile technique and in vivo retention times as well as development of delivery systems for drugs used in the treatment of inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn's disease. An important hypothesis to be tested include the concept that protonated carboxyl groups are vital for bioadhesion, and that these may function effectively on flexible chains such as swollen hydrogel polymer as well as on more rigid chains on bioerodible thermoplastic polymers. To address this issue, we plan to couple three investigative approaches. First, we will conduct direct surface characterization of the various microspheres to quantify the amount of carboxyl groups or any other mucin specific ligands. These studies will be done by using ESCA as well as ATIR. Second, an electrobalance will be used to make direct in vitro measurements of the adhesive forces between polymer microspheres and representative tissues of the GI tract, while maintaining regional pH environments. Third, the direct in vivo evaluation of adhesive, radio-opaque microspheres, retained beyond the normal time of gastrointestinal transit, will be studied through serial X-ray imaging of animals. Overall, the work will consist of the following phases: polymer selection from a pool of synthetic and naturally-occurring polymers; synthesis and characterization of the selected materials; preparation of bioadhesive microspheres carrying barium sulfate, 5-aminosalicylic acid or a combination thereof; bioadhesion studies in vitro; bioadhesion studies in vivo: and in vivo delivery system efficiency tests.