Kandimalla Raghuram, Dash Suvakanta, Bhowal Ashim Chandra, Kalita Sanjeeb, Talukdar Narayan Chandra, Kundu Sarathi, Kotoky Jibon
Drug Discovery Lab, Institute of Advanced Study in Science and Technology.
Girijananda Choudhury Institute of Pharmaceutical Sciences.
Int J Nanomedicine. 2017 Sep 25;12:7025-7038. doi: 10.2147/IJN.S142497. eCollection 2017.
In this study, a glycogen-gold nanohybrid was fabricated to enhance the potency of a promising hepatoprotective agent silymarin (Sly) by improving its solubility and gut permeation. By utilizing a facile green chemistry approach, biogenic gold nanoparticles were synthesized from leaf phytoconstituents in combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron microscopy, UV-Vis spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the successful formation and conjugation of both SGNPs and GSGNPs. The fabricated nanohybrids showed significant protection against CCl-induced hepatic injury in Wistar rats and maintained natural antioxidant (superoxide dismutase and catalase) levels. Animals treated with GSGNPs (10 mg/kg) and SGNPs (20 mg/kg) retained usual hepatic functions with routine levels of hepatobiliary enzymes (aspartate transferase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase) and inflammatory markers (interleukin-1β and tumor necrosis factor-α) with minimal lipid peroxidation, whereas those treated with 100 mg/kg of Sly showed the similar effect. These results were also supported by histopathology of the livers where pronounced hepatoprotection with normal hepatic physiology and negligible inflammatory infiltrate were observed. Significant higher plasma supported the enhanced bioavailability of Sly upon GSGNPs treatment compared to SGNPs and free Sly. Graphite furnace atomic absorption spectrophotometry analysis also substantiated the efficient delivery of GSGNPs over SGNPs. The fabricated therapeutic nanohybrids were also found to be biocompatible toward human erythrocytes and L929 mouse fibroblast cells. Overall, due to increased solubility, bioavailability and profuse gut absorption; GSGNPs demonstrated tenfold enhanced potency compared to free Sly.
在本研究中,制备了一种糖原-金纳米杂化物,通过提高有前景的肝保护剂水飞蓟素(Sly)的溶解度和肠道渗透性来增强其效力。利用简便的绿色化学方法,由叶片植物成分与Sly结合合成了生物源金纳米颗粒(SGNPs)。此外,SGNPs在糖原生物聚合物中聚集,产生治疗性纳米杂化物(GSGNPs)。透射电子显微镜、紫外-可见光谱、X射线衍射和傅里叶变换红外光谱分析证实了SGNPs和GSGNPs的成功形成与结合。制备的纳米杂化物对Wistar大鼠四氯化碳诱导的肝损伤显示出显著的保护作用,并维持了天然抗氧化剂(超氧化物歧化酶和过氧化氢酶)水平。用GSGNPs(10 mg/kg)和SGNPs(20 mg/kg)处理的动物保持了正常的肝功能,肝胆酶(天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶和乳酸脱氢酶)和炎症标志物(白细胞介素-1β和肿瘤坏死因子-α)水平正常,脂质过氧化最小,而用100 mg/kg Sly处理的动物也显示出类似效果。肝脏组织病理学也支持了这些结果,观察到明显的肝保护作用,肝脏生理正常,炎症浸润可忽略不计。与SGNPs和游离Sly相比,GSGNPs处理后血浆中Sly的生物利用度显著提高。石墨炉原子吸收分光光度法分析也证实了GSGNPs比SGNPs具有更有效的递送能力。还发现制备的治疗性纳米杂化物对人红细胞和L929小鼠成纤维细胞具有生物相容性。总体而言,由于溶解度增加、生物利用度提高和肠道吸收丰富,GSGNPs的效力比游离Sly增强了十倍。