Pardhi Vishwas, Chavan Rahul B, Thipparaboina Rajesh, Thatikonda Sowjanya, Naidu Vgm, Shastri Nalini R
Solid State Pharmaceutical Research Group (SSPRG), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India.
Department of Pharmacology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India.
Int J Pharm. 2017 Aug 7;528(1-2):202-214. doi: 10.1016/j.ijpharm.2017.06.007. Epub 2017 Jun 5.
Recent reports on the anticancer potential of niclosamide have opened new avenues for anticancer treatment. Niclosamide belongs to the BCS class II, which is indicative of poor solubility and dissolution rate limited absorption. The aim of this study was to improve the dissolution rate of the drug by mesoporous drug delivery system. Porous silica grades (ordered and nonordered) with different pore size, pore volume and surface area were used in the study. The drug was loaded on silica carriers by the solvent evaporation method and characterized by BET surface area analysis, SEM, P-XRD, DSC, and FTIR. A discriminatory dissolution medium was developed for performing the in vitro dissolution of niclosamide. In comparison to the plain drug, all silica based formulations showed improvement in the dissolution rate. Maximum enhancement in the dissolution rate was observed in 1:2 drug:carrier loading ratio when compared to 1:1 ratio. Different properties of mesoporous silica like structural geometry, pore size and microenvironment pH demonstrated a significant impact on drug release from the formulations. Cytotoxicity of the optimized mesoporous formulations of niclosamide was explored in HCT-116, HCT-15, NCI, MDA-MB-231 and A549 cancer cell lines. Nearly 3 fold and 2 fold increase in% cytotoxicity of drug loaded Syloid-244 and Sylysia 350 at 1:2 ratio respectively, were observed when compared to the plain drug.
最近关于氯硝柳胺抗癌潜力的报道为抗癌治疗开辟了新途径。氯硝柳胺属于BCS II类药物，这表明其溶解度差且溶出速率受限，吸收也受到限制。本研究的目的是通过介孔药物递送系统提高该药物的溶出速率。研究中使用了具有不同孔径、孔体积和表面积的多孔二氧化硅（有序和无序）。药物通过溶剂蒸发法负载在二氧化硅载体上，并通过BET表面积分析、扫描电子显微镜（SEM）、粉末X射线衍射（P-XRD）、差示扫描量热法（DSC）和傅里叶变换红外光谱（FTIR）进行表征。开发了一种鉴别性溶出介质用于进行氯硝柳胺的体外溶出研究。与原料药相比，所有基于二氧化硅的制剂的溶出速率均有提高。与药物与载体1:1的比例相比，在药物与载体1:2的比例下观察到溶出速率的最大提高。介孔二氧化硅的不同性质，如结构几何形状、孔径和微环境pH值，对制剂中药物的释放有显著影响。在HCT-116、HCT-15、NCI、MDA-MB-231和A549癌细胞系中探索了优化后的氯硝柳胺介孔制剂的细胞毒性。与原料药相比，载药的Syloid-244和Sylysia 350在1:2比例下的细胞毒性百分比分别增加了近3倍和2倍。
