Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactide-co-glycolide) (PLGA) nanoparticles
Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactide-co-glycolide) (PLGA) nanoparticles
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DOI：
10.1088/0957-4484/21/28/285104
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发表时间：
2010-07-16
期刊：
影响因子：
3.5
通讯作者：
Warner, Isiah M.
中科院分区：
文献类型：
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作者：
Ganea, Gabriela M.;Fakayode, Sayo O.;Warner, Isiah M.
人们一直在努力开发有效的基于苯醌的抗癌药物，目的是提高水溶性和减少不良反应。百里醌是一种脂溶性的植物化学物质，具有显著的抗氧化和抗癌活性。在这里报道的研究中，合成了负载胸腺醌的PLGA纳米颗粒，并评估了其物理化学，抗氧化和抗癌特性。以阴离子分子胶束为乳化剂，采用乳化溶剂蒸发法合成了纳米粒子。使用Box-Behnken实验设计优化系统以获得最大包封率。发现100 mg PLGA、15 mg TQ和0.5% w/v聚（N-十一碳烯基甘氨酸钠）（聚-SUG）的最佳条件。此外，其他结构相关的分子胶束，如聚（N-庚烯基-甘氨酸钠）（聚-SHG），聚（N-十一碳烯基-亮氨酸钠）（聚-SUL），和聚（N-十一碳烯基-缬氨酸钠）（聚-SUV）作为乳化剂也进行了研究。所有研究的分子胶束提供了优异的乳化剂性能，导致最大优化的TQ包封效率，和单分散粒径低于200 nm。通过透析研究了TQ从分子胶束修饰的纳米粒中的释放，并且达到比游离药物更低的水平。与游离TQ相比，负载TQ的纳米颗粒的抗氧化活性，由IC 50（mg ml（-1）TQ对于50%2，2-二苯基-1-苦基肼（DPPH）清除活性）表示，对于聚SUV乳化的纳米颗粒（0.030 +/- 0.002 mg ml（-1））是最高的。此外，观察到用聚SUV乳化的负载TQ的纳米颗粒比游离TQ更有效地抑制MDA-MB-231癌细胞生长，在96小时后呈现16.0 +/- 5.6%的细胞活力。
Continuous efforts have been made in the development of potent benzoquinone-based anticancer drugs aiming for improved water solubility and reduced adverse reactions. Thymoquinone is a liposoluble benzoquinone-based phytochemical that has been shown to have remarkable antioxidant and anticancer activities. In the study reported here, thymoquinone-loaded PLGA nanoparticles were synthesized and evaluated for physico-chemical, antioxidant and anticancer properties. The nanoparticles were synthesized by an emulsion solvent evaporation method using anionic molecular micelles as emulsifiers. The system was optimized for maximum entrapment efficiency using a Box-Behnken experimental design. Optimum conditions were found for 100 mg PLGA, 15 mg TQ and 0.5% w/v poly(sodium N-undecylenyl-glycinate) (poly-SUG). In addition, other structurally related molecular micelles such as poly(sodium N-heptenyl-glycinate) (poly-SHG), poly(sodium N-undecylenyl-leucinate) (poly-SUL), and poly(sodium N-undecylenyl-valinate) (poly-SUV) were also examined as emulsifiers. All investigated molecular micelles provided excellent emulsifier properties, leading to maximum optimized TQ entrapment efficiency, and monodispersed particle sizes below 200 nm. The release of TQ from molecular micelle modified nanoparticles was investigated by dialysis and reached lower levels than the free drug. The antioxidant activity of TQ-loaded nanoparticles, indicated by IC50 (mg ml(-1) TQ for 50% 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity), was highest for poly-SUV emulsified nanoparticles (0.030 +/- 0.002 mg ml(-1)) as compared to free TQ. In addition, it was observed that TQ-loaded nanoparticles emulsified with poly-SUV were more effective than free TQ against MDA-MB-231 cancer cell growth inhibition, presenting a cell viability of 16.0 +/- 5.6% after 96 h.