Inhaled Delivery of Clofazimine - A High Efficiency, Flow Independent, Targeted, Low Cost DPI

氯法齐明(CFZ) -一种重要的抗结核药物：开发改进的药物方案以缩短多药耐药（MDR）和药敏（DS）结核病（TB）的治疗时间并提高耐受性和安全性是一项非常重要的研究重点。氯法齐明是几十年前批准用于治疗麻风病的药物。该药物用于结核病治疗的动物研究表明，它可以显著缩短治疗时间，特别是在包括PZA在内的联合治疗中。“孟加拉国”方案的有效性为将CFZ纳入耐多药方案可将治疗时间从18个月缩短至9-10个月提供了支持，至少在耐多药其他药物耐药率较低的人群中是如此。然而，口服氯法齐明的耐受性经常受到皮肤变色和胃肠道不良事件的限制。此外，CFZ显著增加QT间期。吸入给药提供了绕过这些屏障的潜力，同时通过在感染的肺组织中获得较高的药物浓度和较低的全身暴露，仍然保持在肺部的有效性，从而增加了立即的效力。目标是开发一种廉价、易于使用的氯法齐明吸入给药系统，与全身抗结核药物联合使用，以改善耐多药耐多药和DS结核病的治疗。

Inhaled Delivery of Clofazimine (CFZ) – An Important Anti-tuberculosis Drug: Development of improved drug regimens to shorten treatment for multidrug-resistant (MDR) and drug susceptible (DS) tuberculosis (TB) and improve tolerance and safety is an extremely high research priority. Clofazimine is a drug approved decades ago for treatment of leprosy. Animal studies of the drug for TB treatment indicate that it may significantly reduce treatment duration, particularly in combinations including PZA. The effectiveness of the “Bangladesh” regimen provides support that inclusion of CFZ in MDR regimens may shorten treatment from 18 to 9-10 months, at least in populations with a low rate of resistance to other MDR drugs. However, tolerance to orally administered clofazimine is often limited by skin discoloration and GI adverse events. In addition, CFZ substantially increased the QT interval. Inhaled delivery offers the potential to bypass these barriers while still maintaining effectiveness in the lungs by achieving high drug concentrations in the infected pulmonary tissue with lower systemic exposure, thus allowing increased immediate potency. The goal is to develop an inexpensive, easy-to-use, inhaled delivery system for clofazimine to be used with combinations of systemic anti-tubercular drugs to improve the treatment of MDR and DS TB.