Department of Clinical Pharmacy, Anhui University of Traditional Chinese Medicine, Hefei 230038, China.
Colloids Surf B Biointerfaces. 2013 Feb 1;102:391-7. doi: 10.1016/j.colsurfb.2012.08.058. Epub 2012 Sep 7.
In this study, Gambogenic acid loaded by solid lipid nanoparticles (GNA-SLNs) was explored to reduce toxicity and improve therapeutic efficacy. GNA-SLNs were prepared by emulsification and low temperature solidification methods, and the freeze-dried powders were then developed to improve the stability. The physical-chemical properties of the products in terms of particle size, zeta potential, morphology and entrapment efficiency were well evaluated. The results revealed that the mean diameter, polydispersivity index (PI), zeta potential, and the entrapment efficiency of the nanoparticles were 163.3 nm, 0.203, -16.9 mV and 61.2%, respectively. In comparion with GNA-SLNs, the freeze-dried solid lipid nanoparticles (SLNs) showed a slight augmentation in the mean particle size (from 163.3 to 173 nm) and PI (from 0.203 to 0.253), and no significant modification in the zeta potential, entrapment efficiency and drug loading. In vitro release kinetics based on a dialysis method demonstrated that Gambogenic acid (GNA) was released in a prolonged fashion for 96 h and followed Higuchi equation unitarily. The release profile did not show any significant modification after the freeze-drying process. The Pharmacokinetic study was carried out, the i.p. administration of GNA formulations to rats at doses of 2.5mg/kg. AUC((0-t)) was increased (up to 3.1-fold) and clearance was decreased (up to 3.03-fold) when GNA entrapped in SLNs. In conclusions, the freeze-dried powders form could enhance the long-term stability of SLN, and solid lipid nanoparticles encapsulation could effectively strategy to change the poor aqueous solubility and prolong the half-life of GNA.
在这项研究中，探讨了用固体脂质纳米粒（GNA-SLNs）负载 Gambogenic 酸，以降低毒性并提高治疗效果。GNA-SLNs 采用乳化低温固化法制备，然后开发了冻干粉末以提高稳定性。从粒径、Zeta 电位、形态和包封效率等方面对产品的物理化学性质进行了很好的评价。结果表明，纳米粒的平均粒径、多分散指数（PI）、Zeta 电位和包封效率分别为 163.3nm、0.203、-16.9mV 和 61.2%。与 GNA-SLNs 相比，冻干固体脂质纳米粒（SLNs）的平均粒径（从 163.3nm 增加到 173nm）和 PI（从 0.203 增加到 0.253）略有增加，Zeta 电位、包封效率和载药量没有明显变化。基于透析法的体外释放动力学研究表明，Gambogenic 酸（GNA）在 96h 内呈延长释放趋势，符合 Higuchi 方程。冻干过程后，释放曲线没有明显变化。进行了药代动力学研究，以 2.5mg/kg 的剂量向大鼠腹腔给予 GNA 制剂。当 Gambogenic 酸被包封在 SLN 中时，AUC((0-t))增加（高达 3.1 倍），清除率降低（高达 3.03 倍）。总之，冻干粉末形式可以提高 SLN 的长期稳定性，而固体脂质纳米粒包封可以有效改变 Gambogenic 酸的水溶性差和延长半衰期。
