Biomedical Engineering Division, Faculty of Chemical Engineering, Tarbiat Modares University, PO Box 14115-114, Tehran, Iran.
Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14174, Iran.
J Biomed Mater Res A. 2017 Oct;105(10):2851-2864. doi: 10.1002/jbm.a.36145. Epub 2017 Jul 14.
Application of many vital hydrophilic medicines have been restricted by blood-brain barrier (BBB) for treatment of brain diseases. In this study, a targeted drug delivery system based on dextran-spermine biopolymer was developed for drug transport across BBB. Drug loaded magnetic dextran-spermine nanoparticles (DS-NPs) were prepared via ionic gelation followed by transferrin (Tf) conjugation as targeting moiety. The characteristics of Tf conjugated nanoparticles (TDS-NPs) were analyzed by different methods and their cytotoxicity effects on U87MG cells were tested. The superparamagnetic characteristic of TDS-NPs was verified by vibration simple magnetometer. Capecitabine loaded TDS-NPs exhibited pH-sensitive release behavior with enhanced cytotoxicity against U87MG cells, compared to DS-NPs and free capecitabine. Prussian-blue staining and TEM-imaging showed the significant cellular uptake of TDS-NPs. Furthermore, a remarkable increase of Fe concentrations in brain was observed following their biodistribution and histological studies in vivo, after 1 and 7 days of post-injection. Enhanced drug transport across BBB and pH-triggered cellular uptake of TDS-NPs indicated that these theranostic nanocarriers are promising candidate for the brain malignance treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2851-2864, 2017.
应用许多重要的亲水性药物已受到血脑屏障 (BBB) 的限制，用于治疗脑部疾病。在这项研究中，基于葡聚糖-精胺的生物聚合物开发了一种靶向药物传递系统，用于药物穿过 BBB 转运。通过离子凝胶化制备载药磁性葡聚糖-精胺纳米粒子 (DS-NPs)，随后用转铁蛋白 (Tf) 作为靶向部分进行共轭。通过不同的方法分析了 Tf 共轭纳米粒子 (TDS-NPs) 的特性，并测试了它们对 U87MG 细胞的细胞毒性作用。通过振动简单磁力计验证了 TDS-NPs 的超顺磁性特征。与 DS-NPs 和游离卡培他滨相比，负载卡培他滨的 TDS-NPs 表现出 pH 敏感性释放行为，对 U87MG 细胞的细胞毒性增强。普鲁士蓝染色和 TEM 成像显示 TDS-NPs 具有显著的细胞摄取。此外，在体内生物分布和组织学研究后，在注射后 1 和 7 天，观察到铁浓度在大脑中显著增加。TDS-NPs 增强了药物穿过 BBB 的转运和 pH 触发的细胞摄取，表明这些治疗性纳米载体是治疗脑恶性肿瘤的有前途的候选药物。 © 2017 威利父子公司。生物医学材料研究杂志 A 部分：105A：2851-2864，2017。
