Uchino Tomonobu, Murata Akiko, Miyazaki Yasunori, Oka Toshihiko, Kagawa Yoshiyuki
Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka 2) Laboratory of Clinical Pharmacokinetics, Shizuoka General Hospital.
Chem Pharm Bull (Tokyo). 2015;63(5):334-40. doi: 10.1248/cpb.c15-00029.
Liquid crystalline nanoparticles (LCNs) were prepared using glyceryl monooleyl ether (GME) by the modified film rehydration method. Hydrogenated lecithin (HL), 1,3-butylene glycol (1,3-BG), and Poloxamer 407 were used as additives. The prepared LCN formulations were evaluated based on particle size, small-angle X-ray diffraction (SAXS) analysis, (1)H- and (19)F-NMR spectra, and in vitro skin permeation across Yucatan micropig skin. The composition (weight percent) of the LCN formulations were GME-HL-1,3-BG (4 : 1 : 15), 4% GME-based LCN and GME-HL-1,3-BG (8 : 1 : 15), 8% GME-based LCN and their mean particle sizes were 130-175 nm. Flurbiprofen 5 and 10 mg was loaded into 4% GME-based LCN and 8% GME-based LCN systems, respectively. The results of SAXS and NMR suggested that both flurbiprofen-loaded formulations consist of particles with reverse type hexagonal phase (formation of hexosome) and flurbiprofen molecules were localized in the lipid domain through interaction of flurbiprofen with the lipid components. Flurbiprofen transport from the LCN systems across the Yucatan micropig skin was increased compared to flurbiprofen in citric buffer (pH=3.0). The 8% GME-based LCN systems was superior to the 4% GME-based LCN for flurbiprofen transport. Since the internal hexagonal phase in the 8% GME-based LCN systems had a higher degree of order compared to the 4% GME-based LCN in SAXS patterns, the 8% GME-based LCN system had a larger surface area, which might influence flurbiprofen permeation. These results indicated that the GME-based LCN system is effective in improving the skin permeation of flurbiprofen across the skin.
采用甘油单油酸酯（GME）通过改良的薄膜水化法制备了液晶纳米颗粒（LCNs）。氢化卵磷脂（HL）、1,3 - 丁二醇（1,3 - BG）和泊洛沙姆407用作添加剂。基于粒径、小角X射线衍射（SAXS）分析、（1）H - 和（19）F - NMR光谱以及在尤卡坦微型猪皮肤上的体外皮肤渗透对制备的LCN制剂进行了评估。LCN制剂的组成（重量百分比）为GME - HL - 1,3 - BG（4∶1∶15）、4%基于GME的LCN和GME - HL - 1,3 - BG（8∶1∶15）、8%基于GME的LCN，它们的平均粒径为130 - 175 nm。分别将5 mg和10 mg氟比洛芬负载到4%基于GME的LCN和8%基于GME的LCN系统中。SAXS和NMR的结果表明，两种负载氟比洛芬的制剂均由具有反相六方相（形成六棱柱体）的颗粒组成，并且氟比洛芬分子通过氟比洛芬与脂质成分的相互作用定位于脂质域中。与柠檬酸缓冲液（pH = 3.0）中的氟比洛芬相比，氟比洛芬从LCN系统穿过尤卡坦微型猪皮肤的转运增加。8%基于GME的LCN系统在氟比洛芬转运方面优于4%基于GME的LCN。由于在SAXS图谱中，8%基于GME的LCN系统中的内部六方相比4%基于GME的LCN具有更高的有序度，8%基于GME的LCN系统具有更大的表面积，这可能影响氟比洛芬的渗透。这些结果表明，基于GME的LCN系统在改善氟比洛芬经皮渗透方面是有效的。
