Kaur Bhavneet, Kaur Maninder, Ahlawat Priyanca, Sharma Sadhna
Department of Biochemistry, Post Graduate Institute of Medical Education and Research, 160012 Chandigarh, India.
Indian J Clin Biochem. 2023 Oct;38(4):466-474. doi: 10.1007/s12291-022-01062-8. Epub 2022 Sep 6.
Combination therapy may counter the risk caused by efflux pumps mediated resistance developed by mycobacteria with a concomitant increase of the bactericidal effect of anti-TB drugs. In the present study, combination of two drugs in a nanoformulation was prepared. Clofazimine targets type 2 NADH dehydrogenase of the electron transport chain, and Verapamil inhibits various mycobacterial efflux pumps. The nanotechnology approach was adopted to overcome limitations associated with administration of free form of drugs by using poly (D, L-lactic-co-glycolic acid) as a polymer. Nanoparticles were prepared by oil/water single emulsion solvent evaporation procedure and characterized by various techniques. The results thus highlighted that developed nanoparticles were spherical with nano range size (200-450 nm). Fourier transform infrared spectroscopy revealed successful encapsulation of drugs in developed nanoformulations. Drugs in combination showed higher encapsulation efficiency and percentage drug loading capacity as compared to individual drug nanoformulations. Also, reduced toxicity of nanoformulation was observed in hemolysis assay as compared to free drugs. analysis demonstrated efficient uptake of rhodamine encapsulated nanoparticles by THP-1 cells, while results revealed sustained drug release of nanoformulation as compared to free drugs in combination. Therefore, we were able to achieve development of a single nanoformulation encapsulating Clofazimine and Verapamil in combination. Based on these findings, future studies can be designed to explore the potential of co-encapsulated Clofazimine and Verapamil nanoparticles in management of tuberculosis.
The online version contains supplementary material available at 10.1007/s12291-022-01062-8.
联合治疗可能会对抗由分枝杆菌外排泵介导的耐药性所带来的风险，同时增强抗结核药物的杀菌效果。在本研究中，制备了一种包含两种药物的纳米制剂。氯法齐明作用于电子传递链的2型烟酰胺腺嘌呤二核苷酸脱氢酶，维拉帕米可抑制多种分枝杆菌外排泵。采用纳米技术方法，以聚（D，L-乳酸-共-乙醇酸）为聚合物，克服了游离药物给药相关的局限性。通过油/水单乳液溶剂蒸发法制备纳米颗粒，并采用多种技术对其进行表征。结果突出显示，所制备的纳米颗粒呈球形，粒径在纳米范围内（200-450纳米）。傅里叶变换红外光谱表明药物成功包封于所制备的纳米制剂中。与单一药物纳米制剂相比，联合用药的纳米制剂表现出更高的包封效率和载药量百分比。此外，与游离药物相比，纳米制剂在溶血试验中显示出更低的毒性。分析表明，罗丹明包封的纳米颗粒可被THP-1细胞有效摄取，而结果显示，与游离药物联合使用相比，纳米制剂具有持续的药物释放特性。因此，我们成功开发出一种同时包封氯法齐明和维拉帕米的单一纳米制剂。基于这些发现，未来的研究可设计用于探索共包封氯法齐明和维拉帕米的纳米颗粒在结核病治疗中的潜力。
在线版本包含可在10.1007/s12291-022-01062-8获取的补充材料。
