Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Int J Pharm. 2013 Jul 15;451(1-2):92-4. doi: 10.1016/j.ijpharm.2013.04.050. Epub 2013 Apr 24.
A pharmacokinetic study was performed in rats to evaluate the oral absorption ratios of nanoparticle suspensions containing the poorly water-soluble compound nifedipine (NI) and two different types of lipids, including hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol. NI-lipid nanoparticle (LN) suspensions with a mean particle size of 48.0 nm and a zeta potential of -57.2 mV were prepared by co-grinding combined with a high-pressure homogenization process. The oral administration of NI-LN suspensions to rats led to a significant increase in the NI plasma concentration, and the area under the curve (AUC) value was found to be 108 min μg mL⁻¹, indicating a 4-fold increase relative to the NI suspensions. A comparison of the pharmacokinetic parameters of the NI-LN suspensions with those of the NI solution prepared using only the surfactant polysorbate 80 revealed that although the AUC and bioavailability (59%) values were almost identical, a rapid absorption rate was still observed in the NI-LN suspensions. These results therefore indicated that lipid nanoparticles prepared using only two types of phospholipid with a mean particle size of less than 50 nm could improve the absorption of the poorly water-soluble drug.
在大鼠中进行了一项药代动力学研究，以评估含有难溶性化合物硝苯地平（NI）的纳米颗粒混悬剂的口服吸收比，该混悬剂含有两种不同类型的脂质，包括氢化大豆卵磷脂和二棕榈酰磷脂酰甘油。通过共研磨结合高压匀质工艺制备平均粒径为 48.0nm、zeta 电位为-57.2mV 的 NI-脂质纳米颗粒（LN）混悬剂。向大鼠口服给予 NI-LN 混悬剂可显著增加 NI 的血浆浓度，曲线下面积（AUC）值为 108minμgmL⁻¹，表明与 NI 混悬剂相比增加了 4 倍。将 NI-LN 混悬剂的药代动力学参数与仅使用表面活性剂聚山梨酯 80 制备的 NI 溶液的药代动力学参数进行比较，结果表明，尽管 AUC 和生物利用度（59%）值几乎相同，但在 NI-LN 混悬剂中仍观察到快速吸收速率。这些结果表明，使用仅两种平均粒径小于 50nm 的磷脂制备的脂质纳米颗粒可以提高难溶性药物的吸收。
