College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 21936, South Korea.
Pharm Res. 2019 Jul 26;36(10):138. doi: 10.1007/s11095-019-2672-x.
This study aimed to incorporate ondansetron hydrochloride (ODS), a water-soluble drug into nanostructured lipid carriers (NLCs) to improve the pharmacokinetic properties of the drug.
NLCs were produced by solvent injection method. Various parameters of formulation and process were assessed to enhance the drug incorporation into NLCs. Physicochemical analyses, in vitro drug release, and pharmacokinetic studies were performed.
Entrapment efficiency (EE) of ODS was considerably improved (>90%) by increasing pH of the aqueous phase. The use of an appropriate level of liquid lipid resulted in small, monodispersed NLCs with the enhanced EE and drug loading (DL). The optimized NLCs formulation exhibited particle size of 185.2 ± 1.9 nm, polydispersity index of 0.214 ± 0.006, EE of 93.2 ± 0.5%, and DL of 10.43 ± 0.05% as well as an in vitro sustained-release profile of ODS. Differential scanning calorimetry and X-ray powder diffraction suggested the amorphous state of ODS in the NLCs. The pharmacokinetic study in rats exhibited the sustained-release characteristic of the optimized ODS-loaded NLCs following subcutaneous administration with an extended T and mean residence time as well as the enhanced systemic exposure compared to the ODS solution.
The ODS-loaded NLCs appear potential for prolongation of drug action and reduction in dosing frequency.
本研究旨在将水溶性药物盐酸昂丹司琼（ODS）包载入纳米结构脂质载体（NLCs）中，以改善药物的药代动力学性质。
采用溶剂注入法制备 NLCs。评估了制剂和工艺的各种参数，以提高药物在 NLCs 中的包封率。进行了物理化学分析、体外药物释放和药代动力学研究。
通过提高水相的 pH 值，ODS 的包封效率（EE）得到了显著提高（>90%）。适当水平的液体脂质的使用导致具有增强的 EE 和药物载量（DL）的小单分散 NLCs。优化的 NLCs 制剂表现出 185.2±1.9nm 的粒径、0.214±0.006 的多分散指数、93.2±0.5%的 EE 和 10.43±0.05%的 DL，以及 ODS 的体外持续释放特性。差示扫描量热法和 X 射线粉末衍射表明 ODS 在 NLCs 中呈无定形态。在大鼠中的药代动力学研究表明，与 ODS 溶液相比，皮下给予优化的 ODS 载 NLCs 具有延长的 T 和平均停留时间以及增强的系统暴露，表现出持续释放的特征。
ODS 载 NLCs 有望延长药物作用时间并减少给药频率。
