Hanafi-Bojd Mohammad Yahya, Jaafari Mahmoud Reza, Ramezanian Navid, Xue Min, Amin Mohamadreza, Shahtahmassebi Nasser, Malaekeh-Nikouei Bizhan
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Eur J Pharm Biopharm. 2015 Jan;89:248-58. doi: 10.1016/j.ejpb.2014.12.009. Epub 2014 Dec 13.
Recent studies with inorganic nanoparticles modified with functional groups have demonstrated improvement in drug delivery into cancer cells. In the present study, we prepared, characterized, and evaluated mesoporous silica nanoparticles (MSNs) as carriers for epirubicin hydrochloride (EPI) in order to improve the antitumor efficacy of this drug. MSNs were prepared and functionalized with phosphonate, polyethylene glycol (PEG) and polyethylenimine-polyethylene glycol (PEI-PEG) groups. Different nanoparticulate formulations were loaded with EPI. The in vitro cytotoxicity and the in vivo antitumor efficacy of MSNs containing EPI were evaluated versus free EPI. The EPI release from nanoparticles was shown to be pH-dependent. The size of MSNs functionalized with polyethyleneimine-polyethylene glycol (MSN-PEI-PEG) was 123.8 ± 4.8 nm. This formulation showed the best antitumor effects at an EPI dose of 9 mg/kg in C-26 colon carcinoma model. The biodistribution results proved that MSN-PEI-PEG-EPI had a higher tumor accumulation compared to free EPI, 3h after drug administration. The results indicated that this formulation could be effective nanocarriers for anti-tumor therapies.
近期对经官能团修饰的无机纳米颗粒的研究表明,其在将药物递送至癌细胞方面有所改善。在本研究中,我们制备、表征并评估了介孔二氧化硅纳米颗粒(MSNs)作为盐酸表柔比星(EPI)的载体,以提高该药物的抗肿瘤疗效。制备了MSNs并用膦酸酯、聚乙二醇(PEG)和聚乙烯亚胺 - 聚乙二醇(PEI - PEG)基团进行功能化修饰。用不同的纳米颗粒制剂负载EPI。对含EPI的MSNs的体外细胞毒性和体内抗肿瘤疗效与游离EPI进行了评估。结果表明纳米颗粒中EPI的释放具有pH依赖性。用聚乙烯亚胺 - 聚乙二醇功能化修饰的MSNs(MSN - PEI - PEG)的尺寸为123.8±4.8 nm。在C - 26结肠癌模型中,该制剂在EPI剂量为9 mg/kg时显示出最佳的抗肿瘤效果。生物分布结果证明,给药3小时后,与游离EPI相比,MSN - PEI - PEG - EPI在肿瘤中的蓄积更高。结果表明该制剂可能是抗肿瘤治疗的有效纳米载体。