MOLECULAR AND CELLULAR TRANSPORT IN MUCUS

粘液中的分子和细胞运输

• 批准号: 2182237
• 负责人: W. Mark Saltzman
• 金额: $ 21.99万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2182237
• 关键词: Alphaherpesvirinae; active immunization; antiviral antibody; chlorhexidine; copolymer; dextrans; ferritin; genital herpes; genital secretion; gluconate; human subject; laboratory mouse; laboratory rabbit; lactate dehydrogenases; leukocytes; monoclonal antibody; mucosa; mucus; neutralizing antibody; nonhuman therapy evaluation; passive immunization; polyacrylate; reproductive system pharmacology; spermicide; vagina

Mucus epithelia in the intestine, lung, mouth, eye, and vagina provide an effective and essential barrier against the entry of pathogens and toxins. Since these epithelia are readily accessible from outside the body, they also represent valuable sites for drug delivery. Here, we propose to continue our bioengineering studies of the ability of molecules and cells to function in and penetrate the mucus coat that protects these tissues. The ultimate goal is to use our findings to design methods for the controlled delivery of antibodies (Ab) or vaccinogens (Vg) directly to a mucus epithelium: Ab to provide passive immunoprotection, Vg to stimulate active immunoprotection. Specifically, biocompatible polymeric controlled release devices will be designed to continuously deliver macromolecules, like Ab and Vg, to mucus layers over a thirty day period. The present studies will focus on a) the distribution and bioavailability of AB and Bg molecules to penetrate and function in mucus samples collected at different times during the menstrual cycle. Since macrophages and other phagocytic cells can transport pathogens and molecules across mucus layers, the ability of phagocytic cells to crawl in mucus will studied, as well as the ability of mucus and Ab to interfere with phagocyte migration and adhesion to epithelial tissues. Mathematical methods will be used to correlate our in vitro and in vivo results, to enhance the value of in vitro methods for optimizing devices for use in vivo. All of the information collected from these basic studies will be used to design improved controlled release polymers for the localized and extended delivery of Ab or Vg to mice and rabbits. Finally, these polymers will be used to test the efficacy of controlled delivery for sustained protection against infectious disease (vaginal herpes virus infections) or unwanted pregnancy (immunocontraception).

肠道，肺，嘴，眼和阴道中的粘液上皮 有效且必不可少的障碍，可抵抗病原体的进入 毒素。 由于这些上皮很容易从外部访问 身体，它们也代表了用于药物输送的宝贵地点。 在这里，我们 提议继续我们的生物工程研究 分子和细胞在运行并穿透粘液涂层 保护这些组织。 最终目标是利用我们的发现 用于控制抗体（AB）或 疫苗（VG）直接到粘液上皮：AB以提供被动 免疫保护，VG以刺激主动免疫保护。 具体来说， 生物相容性聚合控制的释放设备将设计为 连续将大分子（如AB和VG）传递到粘液层 三十天。 目前的研究将重点放在a） AB和BG分子的分布和生物利用度渗透和 在在不同时间收集的粘液样品中的功能 月经周期。 由于巨噬细胞和其他吞噬细胞可以 将病原体和分子跨粘液层， 将研究吞噬细胞在粘液中爬行的细胞以及能力 粘液和AB干扰吞噬细胞的迁移和粘附 上皮组织。 数学方法将用于将我们的 体外和体内结果，以增强体外方法的价值 用于优化用于体内的设备。 收集的所有信息 通过这些基础研究将用于设计改进的受控 释放聚合物，用于将AB或VG的局部和扩展递送到 老鼠和兔子。 最后，这些聚合物将用于测试 受控交付的功效以持续保护 传染病（阴道疱疹病毒感染）或不必要的 怀孕（免疫感应）。