Mannosylated chitosan-decorated PLGA nanoparticles for targeted pulmonary delivery of isoniazid: a promising approach in the treatment of tuberculosis

Tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i> (M. tb), represents a significant challenge to global health. The management of the disease requires an extended course of antibiotic therapy, spanning a duration of 6 to 9 months. The complexity and duration of these regimens frequently lead to significant adverse effects, gastrointestinal issues, and the development of drug resistance. To address these challenges, the nanoparticulate based inhalable drug delivery system was designed as such by synthesising mannosylated chitosan decorated PLGA nanoparticles loaded with isoniazid (MC-PLGA-INH-PNPs) for targeted pulmonary delivery. Hence, nanoparticle based drug delivery system offers the potential to target and deliver the loaded drug directly into the M.tb infected cells. The prepared and optimised nano-formulation had a particle size of 154.9 ± 21 nm, zeta potential −23.2 ± 0.52 mV and entrapment efficiency of 79.8% ± 0.45. Additionally, the MC-PLGA-INH-PNPs exhibited a sustained drug release profile at physiological pH 7.4 for a period of 24 hr. An <i>in vivo</i> study of the MC-PLGA-INH-PNPs was performed on a mouse model utilising lipopolysaccharide as an inducer. The data obtained from the <i>in vivo</i> studies showed substantial improvements in lung tissues architecture and reduced inflammation. The group of animals treated with the MC-PLGA-INH-PNPs showed significant improvement in restoration of the disease when compared to pure drug treated group. These findings further indicate that these inhalable MC-PLGA-INH-PNPs hold a promising strategy for the treatment of tuberculosis and considerably improves pulmonary drug delivery to the target site. However, detailed investigations and testing of this nano-formulation on other relevant animal models will be essential to successfully translate this concept from laboratory to clinical practice.

结核分枝杆菌（Mycobacterium tuberculosis, M. tb）引发的结核病（Tuberculosis, TB）是全球公共卫生领域的重大挑战。该病的临床治疗需采用6~9个月的长疗程抗生素疗法，而此类给药方案的复杂性与较长周期常引发严重不良反应、胃肠道不适，并诱导耐药菌株产生。为应对上述临床难题，本研究设计了基于纳米颗粒的可吸入给药系统：通过合成载有异烟肼（isoniazid）的甘露糖基化壳聚糖修饰PLGA纳米颗粒（mannosylated chitosan decorated PLGA nanoparticles loaded with isoniazid, MC-PLGA-INH-PNPs），实现肺部靶向递送。此类纳米颗粒给药系统可将负载药物精准递送至结核分枝杆菌感染的细胞中，具备良好的应用潜力。本研究制备并优化得到的纳米制剂粒径为154.9±21 nm，zeta电位为-23.2±0.52 mV，包封率达79.8%±0.45%。此外，MC-PLGA-INH-PNPs在生理pH 7.4环境下可实现长达24小时的持续药物释放。本研究以脂多糖（lipopolysaccharide）为诱导剂，在小鼠模型上开展了MC-PLGA-INH-PNPs的体内（in vivo）研究。体内实验结果显示，该纳米制剂可显著改善肺组织结构并减轻炎症反应。与单纯药物治疗组相比，MC-PLGA-INH-PNPs治疗组的疾病恢复效果更为显著。上述研究结果表明，此类可吸入MC-PLGA-INH-PNPs是一种极具前景的结核病治疗策略，可有效提升靶向部位的肺部药物递送效率。不过，为推动该纳米制剂从实验室研究向临床实践转化，仍需在其他相关动物模型中开展更为深入的验证与研究。