Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, NSW 2006, Australia.
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Jordan, Amman 1192, Jordan.
Adv Drug Deliv Rev. 2016 Jul 1;102:83-101. doi: 10.1016/j.addr.2016.05.011. Epub 2016 May 17.
Tuberculosis (TB) is an intracellular infectious disease caused by the airborne bacterium, Mycobacterium tuberculosis. Despite considerable research efforts, the treatment of TB continues to be a great challenge in part due to the requirement of prolonged therapy with multiple high-dose drugs and associated side effects. The delivery of pharmacological agents directly to the respiratory system, following the natural route of infection, represents a logical therapeutic approach for treatment or vaccination against TB. Pulmonary delivery is non-invasive, avoids first-pass metabolism in the liver and enables targeting of therapeutic agents to the infection site. Inhaled delivery also potentially reduces the dose requirement and the accompanying side effects. Dry powder is a stable formulation of drug that can be stored without refrigeration compared to liquids and suspensions. The dry powder inhalers are easy to use and suitable for high-dose formulations. This review focuses on the current innovations of inhalable dry powder formulations of drug and vaccine delivery for TB, including the powder production method, preclinical and clinical evaluations of inhaled dry powder over the last decade. Finally, the risks associated with pulmonary therapy are addressed. A novel dry powder formulation with high percentages of respirable particles coupled with a cost effective inhaler device is an appealing platform for TB drug delivery.
结核病(TB)是一种由空气中的细菌结核分枝杆菌引起的细胞内感染性疾病。尽管进行了大量研究,但结核病的治疗仍然是一个巨大的挑战,部分原因是需要长期使用多种高剂量药物进行治疗,并伴有相关的副作用。将药理制剂直接通过自然感染途径递送至呼吸系统,是治疗或预防结核病的一种合理的治疗方法。肺部给药是非侵入性的,避免了肝脏的首过代谢,并能将治疗剂靶向感染部位。吸入给药还可能降低剂量要求和伴随的副作用。干粉是一种稳定的药物制剂,与液体和混悬剂相比,可以在不冷藏的情况下储存。干粉吸入器易于使用,适合高剂量制剂。本文综述了目前用于结核病的可吸入干粉药物和疫苗输送的创新,包括过去十年中干粉生产方法、吸入干粉的临床前和临床评估。最后,还讨论了与肺部治疗相关的风险。具有高比例可吸入颗粒的新型干粉制剂与具有成本效益的吸入器装置相结合,是结核病药物输送的一个有吸引力的平台。