AEROSOL THERAPY FOR M TUBERCULOSIS INFECTION

描述（改编自申请人摘要）分枝杆菌 结核病（Mtb）通过呼吸道感染， 被肺泡巨噬细胞吸收并在细胞内增殖。 Mtb的抗生素治疗是口服的。该方法 通常成功，但由于器官毒性而发生并发症， 不服从不遵守特别重要，因为 不适当的治疗可能有利于抗生素耐药性的发展， 结核分枝杆菌菌株通过雾化治疗结核分枝杆菌感染 技术可以提供一种有效的方法来浓缩抗生素 从而潜在地降低全身副作用， 或改善依从性，如果抗Mtb活性的功效可以 设计了更短的治疗计划。脂质体技术是 一种提高雾化吸入抗结核杆菌活性的潜在方法， 因为脂质体优先被吞噬细胞吸收， 携带结核分枝杆菌和脂质体的巨噬细胞也可以延长药物的 半衰期气雾剂疗法可能特别有用， 治疗或用于治疗易感个体中的急性Mtb暴露 当结核分枝杆菌可能局限于肺部时。这些调查人员 在小鼠中开发了毒性Mtb肺感染模型。他们打算 应用该模型雾化抗结核药物并确定： (1)用于将药物递送到较低层的颗粒的最佳尺寸 （2）器官分布和细胞内定位， 放射自显影技术;（3）药物分析 使用高效液相色谱法将药物雾化。其他 实验将确定是否雾化抗结核药物 药物可以在感染Mtb的不同阶段杀死Mtb 感染，并确定最大的结核分枝杆菌负担， 药物治疗有效。他们还将比较 雾化的可溶性和脂质体相关抗生素， 感染的免疫活性和免疫缺陷小鼠的Mtb， 确定Mtb治疗是否需要免疫应答 在雾化治疗期间感染。另一个目标是研究一个角色， 用于雾化已知的Mo活化细胞因子和效应分子 增强结核病防御能力这些技术可以作为一种可行的 增强宿主抗结核分枝杆菌和补体的抗性的方法 免疫功能低下宿主的抗生素治疗。

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.