Nanomedicine and Biomaterial Lab., Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 Azar St, Enqelab Sq, Tehran 1417614411, Iran.
Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 AzarSt, Enqelab Sq, Tehran 1417614411, Iran.
Carbohydr Polym. 2016 Jun 25;144:371-81. doi: 10.1016/j.carbpol.2016.01.026. Epub 2016 Jan 25.
To develop a nanoparticulate drug carrier for targeting of the inflamed intestinal mucosa, amphiphilic hyaluronic acid (HA) conjugates were synthesized, which could form self-assembled nanoparticles (NPs) in aqueous solution and budesonide (BDS) was loaded into the HANPs. Their particle sizes were in the range of 177 to 293nm with negative surface charge. The model of inflammatory CACO-2 cells was utilized to investigate the therapeutic potential of budesonide loaded HA nanocarriers. The highest expression of CD44 receptors was found on inflamed Caco-2 cells, as determined by flow cytometry. FITC-labeled HANPs revealed greater uptake in inflamed CACO-2 cells compared to untreated CACO-2 and CD44-negative cell lines, NIH3T3. BDS loaded HANPs displayed almost no toxicity indicating HANPs are excellent biocompatible nano-carriers. BDS loaded HANPs demonstrated higher anti-inflammatory effect on IL-8 and TNF-α secretion in inflamed cell model compared to the same dose of free drug. These results revealed the promising potential of HA nanoparticles as a targeted drug delivery system for IBD treatment.
为了开发一种靶向炎症肠道黏膜的纳米药物载体,合成了两亲性透明质酸(HA)缀合物,其在水溶液中可以形成自组装纳米颗粒(NPs),并将布地奈德(BDS)载入 HANPs。它们的粒径在 177 至 293nm 之间,带负电荷。利用炎症性 CACO-2 细胞模型研究了载有布地奈德的 HA 纳米载体的治疗潜力。通过流式细胞术确定,在炎症 CACO-2 细胞上发现了最高表达的 CD44 受体。FITC 标记的 HANPs 在炎症 CACO-2 细胞中的摄取量明显高于未处理的 CACO-2 和 CD44 阴性细胞系 NIH3T3。载有 BDS 的 HANPs 显示出几乎没有毒性,表明 HANPs 是极好的生物相容性纳米载体。与相同剂量的游离药物相比,载有 BDS 的 HANPs 在炎症细胞模型中对 IL-8 和 TNF-α 分泌表现出更高的抗炎作用。这些结果表明,HA 纳米颗粒作为一种靶向 IBD 治疗的药物递送系统具有广阔的应用前景。