ADHESIVE MICROSPHERES FOR TREATING BOWEL DISEASES

我们建议开发新的生物黏附微球，这将作为 胃肠道疾病的口服给药系统。 该项目涉及体外生物黏附之间的相关性 利用特殊拉伸技术和活体测量的性能 药物保留时间和给药系统的发展 在治疗炎症性肠病(IBD)中，如溃疡性 结肠炎和克罗恩病。需要检验的一个重要假设包括 质子化的羧基对生物黏附至关重要的概念，以及 它们可以在灵活的链上有效地发挥作用，比如膨胀 水凝胶聚合物以及更多刚性链上的生物可腐蚀性 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，我们将直接进行表面 各种微球的表征以定量测定其量 羧基或任何其他粘蛋白特异性配体。这些研究将是 通过使用ESCA和ATIR来完成。其次，将使用电子天平 在体外直接测量粘附力 聚合物微球和具有代表性的胃肠道组织，而 维护区域pH环境。第三，直接的体内评价 粘附性，放射不透明的微球，保留时间超过正常时间 胃肠道转运，将通过系列X射线成像进行研究 动物。总的来说，这项工作将包括以下几个阶段：聚合物 从合成和自然生成的聚合物池中进行选择； 所选材料的合成和表征；制备 携带硫酸钡、5-氨基水杨酸或 它们的组合；体外生物黏附研究；生物黏附研究 体内：体内给药系统效率测试。

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.