Fang Yi-Ping, Lin Yin-Ku, Su Yu-Han, Fang Jia-You
Department of Biotechnology, Yuanpei University, Hsinchu, Taiwan.
Chem Pharm Bull (Tokyo). 2011;59(2):266-71. doi: 10.1248/cpb.59.266.
Tryptanthrin is an ancient medicine which recently was also found to have a function of downregulating multidrug resistance (MDR). However, tryptanthrin is insoluble in water, which limits its availability for delivery into cancer cells. There is a need to improve delivery systems to increase the inhibition of MDR. The aim of this study was to employ nanoparticles encapsulating tryptanthrin to improve the delivery and promote the sustained release of this drug. The approach was to encapsulate tryptanthrin in various nanoparticles, including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid emulsions (LEs). We compared the particle size and zeta potential of these nanoparticles, and evaluated the partitioning behavior of tryptanthrin in them. We also determined the release kinetics of tryptanthrin from these nanoparticles. Moreover, cellular cytotoxicity toward and uptake of tryptanthrin-loaded nanoparticles by human breast cancer cells were determined. We found that the mean particle size of NLCs was lower, and the partition coefficient was higher than those of SLNs, and an increased tryptanthrin release rate was found with the NLC delivery system. NLCs achieved the sustained release of tryptanthrin without an initial burst. In particular, the NLC-C formulation, composed of a mixture of Compritol and squalene as the core materials, showed the highest release rate and cytotoxic effect. Confocal laser scanning microscopic images confirmed drug internalization into cells which enhanced the endocytosis of the particles. These results suggested that NLCs can potentially be exploited as a drug carrier for topical or intravenous use in the future.
靛玉红是一种古老的药物，最近还发现它具有下调多药耐药性（MDR）的功能。然而，靛玉红不溶于水，这限制了它进入癌细胞的可用性。需要改进给药系统以增强对MDR的抑制作用。本研究的目的是采用包裹靛玉红的纳米颗粒来改善药物递送并促进该药物的持续释放。方法是将靛玉红包裹在各种纳米颗粒中，包括固体脂质纳米粒（SLN）、纳米结构脂质载体（NLC）和脂质乳剂（LE）。我们比较了这些纳米颗粒的粒径和zeta电位，并评估了靛玉红在其中的分配行为。我们还测定了靛玉红从这些纳米颗粒中的释放动力学。此外，还测定了载有靛玉红的纳米颗粒对人乳腺癌细胞的细胞毒性和摄取情况。我们发现，NLC的平均粒径较小，分配系数高于SLN，并且NLC给药系统的靛玉红释放速率增加。NLC实现了靛玉红的持续释放且无初始突释。特别是，由Compritol和角鲨烯的混合物作为核心材料组成的NLC-C制剂显示出最高的释放速率和细胞毒性作用。共聚焦激光扫描显微镜图像证实药物内化进入细胞，这增强了颗粒的内吞作用。这些结果表明，NLC未来有可能被用作局部或静脉给药的药物载体。
