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Electrospun poly (L-lactic acid)/gelatine membranes loaded with doxorubicin for effective suppression of glioblastoma cell growth in vitro and in vivo

机译:静电梭孔(L-乳酸)/凝胶膜载有多柔比星用于体外抑制胶质母细胞瘤细胞生长和体内

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摘要

Electrospun membranes are attracting interest as a drug delivery system because of their material composition flexibility and versatile drug loading. In this study, the electrospun membrane was loaded with doxorubicin (DOX) via electrostatic adsorption for long-term drug delivery. DOX loading process was optimized by varying temperature, time, drug concentration, pH and ionic strength of solutions. The loading process did not impair the structural properties of the membrane. Next, we investigated the drug release kinetics using spectroscopic techniques. The composite membranes released 22% of the adsorbed DOX over the first 48 h, followed by a slower and sustained release over 4 weeks. The DOX release was sensitive to acidic solutions that the release rate at pH 6.0 was 1.27 times as that at pH 7.4. The DOX-loaded membranes were found to be cytotoxic to U-87 MG cells in vitro that decreased the cell viability from 82.92% to 25.49% from 24 to 72 h of co-incubation. These membranes showed strong efficacy in suppressing tumour growth in vivo in glioblastoma-bearing mice that decreased the tumour volume by 77.33% compared with blank membrane-treated group on Day 20. In conclusion, we have developed an effective approach to load DOX within a clinically approved poly (L-lactic acid)/gelatine membrane for local and long-term delivery of DOX for the treatment of glioblastoma.
机译:由于其材料组成柔韧性和多功能药物载荷,Electromun膜作为药物输送系统吸引兴趣。在该研究中,通过静电吸附用于长期药物递送的静电吸附,将电纺膜装载用多柔比星(DOX)。通过不同的温度,时间,药物浓度,pH和离子强度进行优化DOX装载过程。装载过程没有损害膜的结构性质。接下来,我们使用光谱技术研究了药物释放动力学。复合膜在前48小时内释放了22%的吸附DOX,然后在4周内越来越慢释放。 DOX释放对酸性溶液敏感,即pH6.0的释放速率为pH 7.4的1.27倍。发现DOX加载的膜是对U-87mg细胞的细胞毒性,在体外,将细胞活力从82.92%降低至25.49%,从24-72小时的共孵育。这些膜表现出强烈的疗效,抑制胶质母细胞瘤的小鼠中体内体内的肿​​瘤生长,与第20天相比将肿瘤体积减少77.33%的肿瘤体积。总之,我们在临床上制定了有效的装载DOX方法批准的聚(L-乳酸)/明胶膜用于DOX的局部和长期递送,用于治疗胶质母细胞瘤。

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