Curcumin diethyl disuccinate encapsulated in chitosan/alginate nanoparticles for improvement of its in vitro cytotoxicity against MDA-MB-231 human breast cancer cells
Curcumin diethyl disuccinate encapsulated in chitosan/alginate nanoparticles for improvement of its in vitro cytotoxicity against MDA-MB-231 human breast cancer cells
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DOI：
10.1691/ph.2016.6105
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发表时间：
2016-12-01
期刊：
影响因子：
1.6
通讯作者：
Rojsitthisak, P.
中科院分区：
文献类型：
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作者：
Bhunchu, S.;Muangnoi, C.;Rojsitthisak, P.
姜黄素二乙基二琥珀酸酯（CDD）是姜黄素类化合物的琥珀酸酯前药，与姜黄素相比，其在人血浆中具有更好的稳定性和改善的体外细胞毒性。因此，CDD具有作为抗癌剂进一步开发的潜力。本研究采用Box-Behnken统计设计法优化CDD壳聚糖/海藻酸钠纳米粒的处方，以提高CDD的治疗效果。采用水包油乳化-离子凝胶法制备了载CD的壳聚糖/海藻酸钠纳米粒。发现具有0.05：1壳聚糖/海藻酸盐质量比、0.65%（w/v）Pluronic F127和1.5mg/ml CDD的制剂是最佳的。FTIR、TGA和XRD证实了CDD分子在纳米颗粒中的包封。体外细胞毒性和细胞摄取研究表明，与游离CDD相比，负载CDD的壳聚糖/海藻酸钠纳米粒在人乳腺癌MDA-MB-231细胞中具有显著更高的细胞毒性和细胞摄取。物理和化学稳定性研究表明，最佳配制的负载CD的壳聚糖/藻酸盐纳米颗粒在4摄氏度下可稳定3个月。
Curcumin diethyl disuccinate (CDD) is a succinate prodrug of curcuminoids that has better stability in human plasma and improved in vitro cytotoxicity compared to curcumin. Therefore, CDD has the potential for further development as an anticancer agent. In this study, we focused on optimization of the formulation of CDD-loaded chitosan/alginate nanoparticles using Box-Behnken statistical design to enhance the therapeutic efficacy of CDD. Oil-in-water emulsification followed by ionotropic gelification was used to prepare the CDD-loaded chitosan/alginate nanoparticles. A formulation with a 0.05:1 chitosan/alginate mass ratio, 0.65% (w/v) Pluronic F127 and 1.5 mg/ml CDD was found to be optimal. FTIR, TGA and XRD confirmed the encapsulation of CDD molecules in the nanoparticles. In vitro cytotoxicity and cellular uptake studies showed that CDD-loaded chitosan/alginate nanoparticles had significantly higher cytotoxicity and cellular uptake in human breast adenocarcinoma MDA-MB-231 cells, compared to free CDD. Physical and chemical stability studies indicated that the optimally formulated CDD-loaded chitosan/alginate nanoparticles were stable at 4 degrees C for 3 months.