Pharmaceutics Division, Central Drug Research Institute, CSIR, Lucknow 226001, India.
Tuberculosis (Edinb). 2011 Jan;91(1):71-81. doi: 10.1016/j.tube.2010.08.009. Epub 2010 Sep 27.
The lungs have received attention as a portal for drug delivery in tuberculosis (TB) from researchers addressing diverse objectives. These include: (a) targeting alveolar macrophages that harbour TB bacilli; (b) maintaining high drug concentrations in lung tissue; (c) systemic delivery of potent or second-line anti-TB agents; and (d) delivering agents that may change the host-pathogen dialectic. Formulation design considerations for each of the above objectives differ in slight, but important ways. As distinct from vaccine delivery formulations, inhalations intended for drug delivery are presumed to require chronic and repeated administration of larger amounts of material. This review seeks to summarize the consensus on the ways and means available or under development, to deliver different anti-TB agents as aerosols for inhalation. These agents include drugs in current clinical use, singly or in combination, experimental chemical entities, siRNA against host molecules, and finally, drugs in clinical use for unrelated pharmacological action, as modifiers of the host-pathogen dialectic. The pharmacokinetics of drug bioavailability in the lung, the blood and other tissues following lung deposition of inhaled therapies are also addressed. Finally, considerations on efficacy studies of drugs administered through aerosol delivery are discussed.
肺部作为结核病（TB）药物输送的门户引起了研究人员的关注，他们的目标各不相同。这些目标包括：（a）针对含有结核分枝杆菌的肺泡巨噬细胞；（b）维持肺部组织中的高药物浓度；（c）全身输送有效或二线抗结核药物；以及（d）输送可能改变宿主-病原体对话的药物。针对上述每一个目标的制剂设计考虑因素略有不同，但非常重要。与疫苗输送制剂不同，预期用于药物输送的吸入剂需要长期和反复给予更大剂量的药物。本综述旨在总结目前或正在开发的将不同抗结核药物作为气雾剂吸入的方式和方法，这些药物包括目前临床使用的单一或联合药物、实验化学实体、针对宿主分子的 siRNA 以及最后，临床用于非相关药理作用的药物，作为宿主-病原体对话的调节剂。还讨论了吸入治疗肺部沉积后药物在肺部、血液和其他组织中的药代动力学和生物利用度。最后，讨论了通过气溶胶给药的药物疗效研究的考虑因素。
