Lin Wen Jen, Duh Yi Shein
Graduate Institute of Pharmaceutical Sciences, School of Pharmacy, National Taiwan University, Taipei, Taiwan; Drug Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Pharmaceutical Sciences, School of Pharmacy, National Taiwan University, Taipei, Taiwan.
Eur J Pharm Biopharm. 2016 Nov;108:297-303. doi: 10.1016/j.ejpb.2016.07.015. Epub 2016 Jul 20.
The aim of this study was to develop nanostructured lipid carriers (NLCs) for transdermal delivery of acid-labile lansoprazole (LPZ). The drug loading, particle size, zeta potential, thermal behavior and stability of NLCs were evaluated. The particle size of NLCs was in the range of 90-210nm and the zeta potential was -61.9 to +3.2mV dependent of the compositions. Stearylamine (SA) prevented lansoprazole degradation and maintained drug stable in NLCs. The anionic sodium dodecyl sulfate (SDS) adsorbed on the lipid surface and formed complex with cationic SA to prevent NLCs aggregation. The effects of type (e.g., isopropyl myristate (IPM), menthol) and concentration (e.g., 1.25, 2.50, 3.75%w/w) of enhancers on penetration of lansoprazole NLC hydrogels were investigated in vitro using Wistar rat skin. The steady-state flux of lansoprazole NLC hydrogel containing 3.75% IPM was the highest which was enhanced by 2.7 folds as compared to enhancer-free NLC hydrogel. In vivo pharmacokinetics of lansoprazole following transdermal delivery of NLC hydrogel showed that the elimination of drug was significantly reduced and the mean residence time of drug was prominently prolonged as compared to intravenous drug solution (p<0.005). The accumulation of drug in the skin and continuous penetration of drug through the skin accounted for the maintenance of drug concentration for at least 24h.
本研究的目的是开发用于酸不稳定型兰索拉唑（LPZ）经皮递送的纳米结构脂质载体（NLCs）。对NLCs的载药量、粒径、zeta电位、热行为和稳定性进行了评估。NLCs的粒径在90 - 210nm范围内，zeta电位为 - 61.9至 + 3.2mV，取决于其组成。硬脂胺（SA）可防止兰索拉唑降解并使药物在NLCs中保持稳定。阴离子十二烷基硫酸钠（SDS）吸附在脂质表面并与阳离子SA形成复合物以防止NLCs聚集。使用Wistar大鼠皮肤在体外研究了增强剂的类型（如肉豆蔻酸异丙酯（IPM）、薄荷醇）和浓度（如1.25、2.50、3.75%w/w）对兰索拉唑NLC水凝胶渗透的影响。含有3.75% IPM的兰索拉唑NLC水凝胶的稳态通量最高，与无增强剂的NLC水凝胶相比提高了2.7倍。NLC水凝胶经皮递送后兰索拉唑的体内药代动力学表明，与静脉注射药物溶液相比，药物消除显著减少，药物平均驻留时间显著延长（p<0.005）。药物在皮肤中的蓄积以及药物持续透过皮肤导致药物浓度至少维持24小时。
