期刊
JOURNAL OF CONTROLLED RELEASE
卷 324, 期 -, 页码 17-33出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2020.05.013
关键词
Mucus penetrating particles; Tuberculosis; Host defence peptide; Pulmonary drug delivery; N-acetyl cysteine; Biofilm inhibition
资金
- SERB-DST, India [YSS/2014/000053, CRG/2019/001483]
- Nano-Mission, India [SR/NM/NS-1123/2016]
- INST
- CSIR, India
Pulmonary drug delivery system is increasingly gaining popularity for several lung diseases including tuberculosis(TB) due to its ability to attain high drug concentrations at the site of infection and to minimize systemic toxicity. In TB therapy, the efficacy of the antibiotics decreases and bacteria becomes resistant in course of time due to the formation of several barriers like lung-mucus and biofilms around the microorganism. The conventional inhalable microparticles(MP) are majorly trapped in dense mucin mess network and quickly cleared by mucocilliary clearance. In this study, we determined whether the anti-TB activity of drug-loaded inhalable polymeric microparticles could be synergized with the mucus-penetrating and biofilm disrupting properties. Mucus-penetrating-microparticles(NAC/PLGA-MPP) were developed combining the benefits of anti-TB drug with host defence peptides(HDP). IDR-1018 peptide was encapsulated with/without an anti-TB drug in N-acetyl cysteine(NAC) decorated porous PLGA microspheres. Aerodynamic parameters(MMAD3.79 +/- 1.04 mu m, FPF-52.9 +/- 5.11%) were optimized for the finest deposition and targeting inside the lungs. The multiple-tracking-technique(MPT) results indicate that the coating of NAC on porous PLGA-MS dramatically increased (4.1fold) the particle transit through the mucus barrier. Designed inhalable NAC/PLGA-MPP do not adhere to lung mucus, disrupt the bacterial biofilm and provide uniform drug delivery to lungs after pulmonary delivery. The formulation was evaluated for activity against M.tb in macrophage cultures and in mice model infected with a low-dose bacterial (similar to 100 CFU) aerosol. The inhalation of NAC/PLGA-MPP encapsulated with IDR-1018 significantly reduced (p<.05) bacterial load (up to similar to 3.02LogCFU/ml) and inflammation in lungs in a mouse model of TB compared to untreated and blank treated animals in 6 weeks of daily dose. The histopathological results validate the compelling chemotherapeutic outcome of inhaled formulations. This data supports the harnessing potential of mucus penetrating inhalable drug delivery systems as a vehicle for targeted lung delivery. This value-added inhalable formulation could be beneficial for resistant TB therapeutics when used as an adjunct to existing DOTS (Directly observed treatment, short-course) therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据