College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, PR China.
College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, PR China.
Int J Pharm. 2015 Jan 15;478(1):60-69. doi: 10.1016/j.ijpharm.2014.11.017. Epub 2014 Nov 12.
The aim of this study was to optimize the process variables of zanamivir-loaded solid lipid nanoparticles (SLNs) and to predict their cellular transport across Caco-2 cell monolayers. Zanamivir-loaded SLNs were prepared by a double emulsion solvent evaporation method. The effects of process variables on the mean particle size and zeta potential of SLNs were investigated and the physicochemical properties of SLNs were characterized. In addition, the cytotoxicity and transport ability of SLNs were also studied in Caco-2 cell model. The mean particle size of drug-loaded SLNs was significantly affected by the process variables. The SLNs were prepared using glyceryl monosterate (1% polyvinyl alcohol (PVA) or 1.5% poloxamer 188 as surfactant) had a regular shape with a relatively lower mean particle size (324.2 and 224.9 nm, respectively), higher encapsulation efficacy (55.7 and 42.4%, respectively) and sustained drug release over 12h. The crystalline form of drug had been partly changed and no physicochemical interaction had occurred between drug and carriers in SLNs. The cell viability was approximately 100% even at a high concentration of blank SLNs. There was no remarkable difference in drug permeation between drug-loaded SLNs and drug solution at 2h, while drug-loaded SLNs showed a significant decrease in drug permeation compared with the drug solution at 4h. The process variables of zanamivir-loaded SLNs were successfully optimized in this study. However, these SLNs significantly reduced the transport ability of zanamivir across Caco-2 cell monolayers. Further studies are needed to fully understand the real absorption mechanism of developed SLNs.
本研究旨在优化扎那米韦负载固体脂质纳米粒（SLN）的工艺变量，并预测其穿过 Caco-2 细胞单层的细胞转运。扎那米韦负载的 SLN 通过双乳液溶剂蒸发法制备。考察了工艺变量对 SLN 平均粒径和 Zeta 电位的影响，并对 SLN 的理化性质进行了表征。此外，还在 Caco-2 细胞模型中研究了 SLN 的细胞毒性和转运能力。载药 SLN 的平均粒径受工艺变量的显著影响。使用甘油单硬脂酸酯（1%聚乙烯醇（PVA）或 1.5%泊洛沙姆 188 作为表面活性剂）制备的 SLN 呈规则形状，平均粒径较小（分别为 324.2nm 和 224.9nm），包封效率较高（分别为 55.7%和 42.4%），药物释放可持续 12 小时以上。药物的晶型已部分改变，药物与载体在 SLN 中未发生物理化学相互作用。即使在高浓度空白 SLN 的情况下，细胞活力也接近 100%。在 2 小时时，载药 SLN 与药物溶液之间的药物渗透没有明显差异，而在 4 小时时，载药 SLN 与药物溶液相比，药物渗透显著减少。本研究成功优化了扎那米韦负载 SLN 的工艺变量。然而，这些 SLN 显著降低了扎那米韦穿过 Caco-2 细胞单层的转运能力。需要进一步研究以充分了解开发的 SLN 的真实吸收机制。
