Development and Characterization of Nanoembedded Microparticles for Pulmonary Delivery of Antitubercular Drugs against Experimental Tuberculosis
Development and Characterization of Nanoembedded Microparticles for Pulmonary Delivery of Antitubercular Drugs against Experimental Tuberculosis
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DOI：
10.1021/acs.molpharmaceut.5b00016
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发表时间：
2015-11-01
影响因子：
4.9
通讯作者：
Gupta, Pushpa
中科院分区：
文献类型：
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作者：
Goyal, Amit Kumar;Garg, Tarun;Gupta, Pushpa
本研究的首要目标是开发和评估利福平（RIF）和异烟肼（INH）负载的喷雾干燥纳米包埋微粒对实验性结核病（TB）的潜力。在这项研究中，RIF-INH加载各种制剂（壳聚糖，瓜尔胶，甘露聚糖，瓜尔胶包衣壳聚糖）通过喷雾干燥制备和表征的基础上，在体外和体内研究。结果表明，与甘露聚糖制剂相比，瓜尔胶喷雾干燥颗粒显示出均匀的粒度分布和光滑的表面。瓜尔胶批次表现出优异的流动性归因于其最佳的水分含量和均匀的粒度分布。药物释放显示出双相释放模式，即，最初的爆发，然后持续释放模式。瓜尔胶包衣制剂的优先摄取表明甘露糖部分存在于巨噬细胞的特定细胞表面并具有选择性摄取能力。体内肺分布研究表明，瓜尔胶包被的壳聚糖（GCNP）批次显示出在靶部位的长期停留，从而提高了药物的治疗效用，并显著降低了全身毒性。与对照组相比，优化的载药GCNP制剂导致杆菌数量减少近5倍。组织学研究还表明，给药组均未显示任何肺组织异常的证据。因此，GCNPs可能是一种有前途的载体，用于选择性地将抗结核药物递送到肺泡巨噬细胞，并且具有最小的副作用，用于有效地管理TB。
The foremost objective of the present research study was to develop and evaluate the potential of rifampicin (RIF) and isoniazid (INH) loaded spray dried nanoembedded microparticles against experimental tuberculosis (TB). In this study, RIF-INH loaded various formulations (chitosan, guar gum, mannan, and guar gum coated chitosan) were prepared by spray drying and characterized on the basis of in vitro as well as in vivo studies. Results showed that guar gum spray dried particles showed uniform size distribution with smooth surface as compare to mannan formulations. Guar gum batches exhibited excellent flow ability attributed to their optimum moisture content and uniform size distribution. The drug release showed the biphasic pattern of release, i.e., initial burst followed by a sustained release pattern. The preferential uptake of guar gum coated formulations suggested the presence and selective uptake capability of mannose moiety to the specific cell surface of macrophages. In vivo lung distribution study showed that guar gum coated chitosan (GCNP) batches demonstrated prolonged residence at the target site and thereby improve the therapeutic utility of drug with a significant reduction in systemic toxicity. Optimized drug loaded GCNP formulation has resulted in almost 5-fold reduction of the number of bacilli as compared to control group. Histopathology study also demonstrated that none of the treated groups show any evidence of lung tissue abnormality. Hence, GCNPs could be a promising carrier for selective delivery of antitubercular drugs to alveolar macrophages with the interception of minimal side effects, for efficient management of TB.