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Mannose receptor targeted bioadhesive chitosan nanoparticles of clofazimine for effective therapy of tuberculosis
Saudi Pharmaceutical Journal ( IF 3.0 ) Pub Date : 2020-10-24 , DOI: 10.1016/j.jsps.2020.10.008
Datta Maroti Pawde 1 , Matte Kasi Viswanadh 1 , Abhishesh Kumar Mehata 1 , Roshan Sonkar 1 , Narendra 1 , Suruchi Poddar 2 , Ankita Sanjay Burande 1 , Abhishek Jha 1 , Kiran Yellappa Vajanthri 2 , Sanjeev Kumar Mahto 2 , V N Azger Dustakeer 3 , Madaswamy S Muthu 1
Affiliation  

Drug-resistant tuberculosis (TB) is one of the most lethal diseases, and it is imperative to exploit an advanced drug formulation for its effective treatment. This work aims to develop a mannose receptor-targeted bioadhesive chitosan nanoparticles for effective drug-resistant tuberculosis treatment. The clofazimine loaded chitosan nanoparticles were formulated; their size, charge, polydispersity (PDI), surface morphology, entrapment efficiency (EE) and in-vitro release pattern were established. Also, cellular uptake study on C2C12 cell lines and anti-mycobacterial activity against H37Rv (a standard strain of Mycobacterium tuberculosis) were evaluated. The particle sizes of formulated chitosan nanoparticles were in the range of 132–184 nm and EE was also found to be between 73 and 95%. The functionalization of bioadhesive chitosan nanoparticles with mannose was confirmed by infrared spectroscopy (FTIR). The uptake studies on the C2C12 cell lines showed that mannosylated nanoparticles were more efficiently internalized when compared to non-targeted nanoparticles. Further, luciferase reporter phage (LRP) assay against H37Rv strain showed that clofazimine nanoparticles were found to be 49.5 times superior in terms of inhibition and anti-mycobacterial activity than free clofazimine. This excellent activity might be attributed to enhanced drug delivery with a promising bioadhesion property of chitosan-based nanoparticles.



中文翻译:

甘露糖受体靶向生物粘附壳聚糖纳米粒氯法齐明有效治疗结核病

耐药结核病(TB)是最致命的疾病之一,开发先进的药物制剂对其进行有效治疗势在必行。本工作旨在开发一种甘露糖受体靶向生物粘附壳聚糖纳米颗粒,用于有效治疗耐药结核病。配制负载氯法齐明的壳聚糖纳米颗粒;确定了它们的尺寸、电荷、多分散性 (PDI)、表面形态、包埋效率 (EE) 和体外释放模式。此外,对 C2C12 细胞系的细胞摄取研究和针对 H37Rv(结核分枝杆菌的标准菌株)的抗分枝杆菌活性) 进行了评估。配制的壳聚糖纳米粒子的粒径范围为 132-184 nm,EE 也被发现在 73% 和 95% 之间。通过红外光谱 (FTIR) 证实了具有甘露糖的生物粘附性壳聚糖纳米颗粒的功能化。对 C2C12 细胞系的吸收研究表明,与非靶向纳米颗粒相比,甘露糖基化纳米颗粒更有效地内化。此外,针对 H37Rv 菌株的荧光素酶报告噬菌体 (LRP) 测定表明,氯法齐明纳米颗粒在抑制和抗分枝杆菌活性方面比游离氯法齐明高 49.5 倍。这种优异的活性可能归因于壳聚糖基纳米粒子具有良好的生物粘附特性的药物递送增强。

更新日期:2020-12-29
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