AEROSOL THERAPY FOR M TUBERCULOSIS INFECTION

分枝杆菌描述(改编自申请人的摘要) 结核病(Mtb)通过有机体所在的呼吸道感染 被肺泡巨噬细胞摄取并在细胞内增殖。 结核分枝杆菌的抗生素治疗是口服的。这种方法是 通常是成功的，但并发症发生是由于器官毒性和 不合规。不遵守规定特别重要，因为 不适当的治疗有利于抗生素抗药性的发展 结核分枝杆菌的菌株。雾化吸入治疗结核分枝杆菌感染 技术可能为浓缩抗生素提供一种有效的手段 在结核杆菌感染的肺部，从而潜在地减少全身副作用， 或改善依从性，如果抗结核活动的效果可以 改进和设计了更短的治疗计划。脂质体技术是 一种提高喷雾剂抗结核分枝杆菌活性的潜在方法 抗生素，因为脂质体优先被吞噬细胞摄取 含有Mtb和脂质体的巨噬细胞也可以延长药物的寿命 半衰期。雾化疗法作为一种预防措施可能特别有用。 治疗或治疗易感人群的急性结核分支杆菌暴露 当结核分枝杆菌可能局限于肺部时。这些调查人员已经 在小鼠身上建立了一种致病性结核分枝杆菌肺部感染模型。他们打算 将该模型应用于抗结核药物的雾化，并确定： (1)向下输送药物的最佳颗粒尺寸 呼吸道；(2)器官分布和细胞内定位 放射自显影技术：以及(3)丹参的药理分析 高效液相色谱雾化药物。其他 实验将确定雾化抗结核是否 在结核杆菌感染的不同阶段，药物可以杀死感染小鼠的结核杆菌 感染，并确定雾化的最大结核分枝杆菌负荷 药物治疗是有效的。他们还将比较其有效性。 雾化可溶抗生素和脂质体相关抗生素，清除 受感染的免疫活性和免疫缺陷小鼠的结核分枝杆菌感染 确定治疗结核分枝杆菌是否需要免疫反应 雾化治疗期间的感染。另一个目标将是检查一个角色 用于雾化已知的钼激活细胞因子和效应分子 以增强本土结核分枝杆菌的防御能力。这些技术可能会成为一种可行的 一种增强宿主对结核分枝杆菌和补体抗性的方法 免疫受损宿主的抗生素治疗。

DESCRIPTION (Adapted from the applicant's abstract) Mycobacterium tuberculosis (Mtb) infects via the respiratory tract where organisms are taken up by alveolar macrophages and proliferate intracellularly. Antibiotic therapy for Mtb is administered orally. This method is usually successful but complications occur due to organ toxicities and noncompliance. Noncompliance is of particular importance because inadequate treatment can favor the development of antibiotic resistant strains of Mtb. Treatment of Mtb infections by aerosolization techniques may provide an effective means for concentrating antibiotics in Mtb-infected lungs thus potentially decreasing systemic side effects, or improving compliance if the efficacy of anti-Mtb activity can be improved and a shorter treatment plan designed. Liposome technology is a potential method for improving anti-Mtb activity of aerosolized antibiotics because liposomes are preferentially taken up by phagocytic macrophages which harbor Mtb and liposomes can also prolong a drug's half-life. Aerosol therapy may be particularly useful as a prophylactic therapy or for treating acute Mtb exposures in susceptible individuals when Mtb is likely localized to the lung. These investigators have developed a virulent Mtb lung infection model in mice. They intend to apply this model for aerosolizing anti-tuberculous drugs and determine: (1) the optimal size of particle for delivering drugs to the lower airways; (2) the organ distribution and intracellular location using autoradiographic techniques: and (3) the pharmacological analysis of aerosolized drugs using high performance liquid chromatography. Other experiments will determine whether aerosolization of anti-tuberculous agents can kill Mtb in infected mice at different stages of Mtb infection and determine the maximal Mtb burden for which aerosolized drug therapy is efficacious. They will also compare the effectiveness of aerosolized soluble and liposome-associated antibiotics, on clearance of Mtb from infected immunocompetent and immunodeficient mice to determine whether the immune response is required for treatment of Mtb infections during aerosol therapy. Another aim will be to examine a role for aerosolizing known Mo activating cytokines and effector molecules to enhance native Mtb defenses. These techniques may serve as a viable method for enhancing host resistance against Mtb and complement antibiotic therapy in immunocompromised hosts.