Department of Pharmaceutical Sciences, Collage of Pharmacy, University of Oklahoma Health Sciences Center Oklahoma City, OK, USA.
Front Cell Infect Microbiol. 2012 Sep 7;2:118. doi: 10.3389/fcimb.2012.00118. eCollection 2012.
Historically, pharmaceutical aerosols have been employed for the treatment of obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease, but in the past decades their use has been expanded to treat lung infections associated with cystic fibrosis and other respiratory diseases. Tuberculosis (TB) is acquired after inhalation of aerosol droplets containing the bacilli from the cough of infected individuals. Even though TB affects other organs, the lungs are the primary site of infection, which makes the pulmonary route an ideal alternative route to administer vaccines or drug treatments. Optimization of formulations and delivery systems for anti-TB vaccines and drugs, as well as the proper selection of the animal model to evaluate those is of paramount importance if novel vaccines or drug treatments are to be successful. Pharmaceutical aerosols for patient use are generated from metered dose inhalers, nebulizers, and dry powder inhalers (DPIs). In addition to the advantages of providing more efficient delivery of the drug, low cost, and portability, pharmaceutical dry powder aerosols are more stable than inhalable liquid dosage forms and do not require refrigeration. Methods to manufacture dry powders in respirable sizes include micronization, spray drying, and other proprietary technologies. Inhalable dry powders are characterized in terms of their drug content, particle size, and dispersibility to ensure deposition in the appropriate lung region and effective aerosolization from the device. These methods will be illustrated as they were applied for the manufacture and characterization of powders containing anti-tubercular agents and vaccines for pulmonary administration. The influence of formulation, selection of animal model, method of aerosol generation, and administration on the efficacy demonstrated in a given study will be illustrated by the evaluation of pharmaceutical aerosols of anti-TB drugs and vaccines in guinea pigs by our group.
从历史上看，药物气溶胶一直被用于治疗阻塞性气道疾病，如哮喘和慢性阻塞性肺疾病，但在过去几十年中，它们的用途已经扩展到治疗与囊性纤维化和其他呼吸道疾病相关的肺部感染。结核病 (TB) 是通过吸入含有感染个体咳嗽中细菌的气溶胶飞沫而获得的。尽管结核病会影响其他器官，但肺部是感染的主要部位，这使得肺部途径成为接种疫苗或药物治疗的理想替代途径。优化抗结核疫苗和药物的配方和输送系统，以及正确选择用于评估这些药物的动物模型，如果要成功开发新型疫苗或药物治疗方法，这一点至关重要。供患者使用的药物气溶胶是由计量吸入器、雾化器和干粉吸入器 (DPIs) 产生的。除了提供更高效的药物输送、低成本和便携性等优点外，药物干粉气溶胶比可吸入的液体剂型更稳定，并且不需要冷藏。制造可吸入干粉的方法包括微粉化、喷雾干燥和其他专有技术。可吸入干粉的特征在于其药物含量、粒径和分散性，以确保在适当的肺部区域沉积并从装置中有效雾化。这些方法将被说明，因为它们被应用于制造和表征含有抗结核药物和疫苗的干粉，用于肺部给药。我们小组通过评估豚鼠的抗结核药物和疫苗的药物气溶胶，说明了制剂、动物模型选择、气溶胶生成方法和给药方式对研究中显示的疗效的影响。
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