Folic acid-chitosan-alginate nanocomplexes for multiple delivery of chemotherapeutic agents
Folic acid-chitosan-alginate nanocomplexes for multiple delivery of chemotherapeutic agents
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DOI：
10.1016/j.jddst.2018.06.020
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发表时间：
2018-10-01
影响因子：
5
通讯作者：
Sedlarik, Vladimir
中科院分区：
文献类型：
--
作者：
Di Martino, Antonio;Trusova, Marina E.;Sedlarik, Vladimir
参与药物递送领域的研究人员所面临的一个主要挑战是开发创新的多药物递送系统。在此，实验重点是制备基于壳聚糖和海藻酸的纳米复合物，目的是分配化疗药物的组合，提高其功效并减少剂量。为了增强靶向，进行与叶酸的缀合。所制备的载体呈现球形，直径在70-120 nm范围内，zeta-电位在30 - 35 mV之间，在人血清中具有良好的稳定性，并且溶血活性低至100 μ g/mL。每毫克载体负载和释放超过800 μ g药物，显示pH依赖性趋势，没有物理、化学和生物干扰，这得益于对给定药物释放具有完全控制的优点。对人宫颈上皮癌细胞和小鼠成纤维细胞进行的体外研究清楚地表明，所述双负载复合物显示出比单负载和游离药物制剂更大的细胞毒性。细胞的活力降低，从而证实了靶向分子发挥的主要作用。
A major challenge faced by researchers involved in the sphere of drug delivery is the development of innovative multidrug delivery systems. Herein, experimentation focused on preparing nanocomplexes based on chitosan and alginic acid with the purpose of allocating a combination of chemotherapeutic drugs, improving their efficacy and reducing dosage. In order to enhance targeting, conjugation with folic acid was performed. The prepared carriers exhibited a spherical shape with a diameter in the range 70-120 nm, a zeta-potential between 30 and 35 mV with good stability in human serum, and low hemolytic activity of up to 100 mu g/mL. Over 800 mu g of drugs per mg of carrier were loaded and released, displaying a pH-dependent trend with no physical, chemical and biological interferences, which benefited from the advantage of having full control over the given release of drug. In vitro studies performed on human epithelial cervix carcinoma cells and mouse fibroblast cells clearly demonstrated that said dual-loaded complexes showed greater cytotoxicity than single-loaded and free-drug formulations. The viability of the cells decreased, thereby confirming the primary role played by the targeting molecule.