ADHESIVE MICROSPHERES FOR TREATING BOWEL DISEASES

用于治疗肠道疾病的粘性微球

• 批准号: 2185099
• 负责人: Edith Mathiowitz
• 金额: $ 15.79万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2185099
• 关键词: Crohn's disease; adhesions; barium; biomaterial development /preparation; biomaterial evaluation; carboxyl group; colitis; copolymer; drug screening /evaluation; gastrointestinal disorder chemotherapy; gastrointestinal pharmacology; infrared spectrometry; interferometry; laboratory rat; ligands; microcapsule; mucins; nonhuman therapy evaluation; oral administration; p aminosalicylate; protonation; radioactive microsphere technique; scanning electron microscopy; sulfates; surface property

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.

我们建议开发新型的生物粘附微球，以作为 胃肠道疾病的口服药物输送系统。 该项目涉及体外生物粘附之间的相关性 使用专门的拉伸技术和体内测量的特性 保留时间以及用于使用药物的输送系统的开发 在治疗炎症性肠病（IBD）中，例如溃疡 结肠炎和克罗恩病。要测试的重要假设包括 质子化羧基对生物粘附至关重要的概念， 这些可能有效地在柔性链（例如肿胀）上起作用 水凝胶聚合物以及更刚性的链上 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 各种微球的表征以量化 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完成。其次，将使用电力 直接在体外测量粘合力 胃肠道的聚合物微球和代表性组织 维持区域pH环境。第三，直接体内评估 粘合剂，射线般的微球，保留在正常时间之外 胃肠道交通将通过串行X射线成像进行研究 动物。总体而言，工作将包括以下阶段：聚合物 从合成和自然出现的聚合物池中选择； 所选材料的合成和表征；准备 携带硫酸钡，5-氨基水杨酸或 组合；体外生物粘附研究；生物粘附研究 体内：体内递送系统效率测试。