Kadhum Wesam R, Hada Tomoki, Hijikuro Ichiro, Todo Hiroaki, Sugibayashi Kenji
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University.
Farnex Incorporated, Tokyo Institute of Technology Yokohama Venture Plaza.
J Oleo Sci. 2017;66(9):939-950. doi: 10.5650/jos.ess17032.
Liquid crystal (LC)-forming lipids represent an important class of biocompatible amphiphiles and their application extends to cosmeceutical, dietary, and pharmaceutical technologies. In the present study, we aimed to develop strategies for designing and optimizing oral and topical LC formulations by evaluating their in vitro and in vivo drug absorption performances. C-Monoglycerol ester (MGE) was used as a LC-forming lipid. p-Amino benzoic acid, methyl PABA, ethyl PABA, and sodium fluorescein were selected as drug models with different physiochemical properties. Various oral and topical LC formulations were designed based on changes in the LC forming lipid contents in the formulations and entrapped with different physiochemical properties of the drugs. The LC phase structures were evaluated using small-angle X-ray scattering (SAXS). The drug-release profiles from LC formulations were determined using a dialysis membrane method. In vivo oral absorption of LC formulations was conducted in Wistar rats. Furthermore, the skin penetration of drugs from LC formulations was investigated by in vitro skin permeation studies. As a result, although the release profile was influenced by changes in MGE concentration, it was more dramatically influenced by changes in the physiochemical properties of the entrapped drugs. Drug absorption after oral and topical administration of LC formulations was dramatically affected by the concentration of MGE. The concentration of LC-forming lipid and the physiochemical properties of entrapped drugs are key issues for good performance of the LC formulations in various pharmaceutical applications. The present results could enable researchers to manipulate LC formulation approaches intended to improve the oral absorption and skin permeation of drugs.
形成液晶（LC）的脂质是一类重要的生物相容性两亲分子，其应用涵盖了药妆、饮食和制药技术。在本研究中，我们旨在通过评估其体外和体内药物吸收性能，开发设计和优化口服及外用LC制剂的策略。单甘油酯（MGE）被用作形成LC的脂质。对氨基苯甲酸、对氨基苯甲酸甲酯、对氨基苯甲酸乙酯和荧光素钠被选为具有不同理化性质的药物模型。基于制剂中形成LC的脂质含量的变化设计了各种口服和外用LC制剂，并包载了具有不同理化性质的药物。使用小角X射线散射（SAXS）评估LC相结构。使用透析膜法测定LC制剂的药物释放曲线。在Wistar大鼠中进行了LC制剂的体内口服吸收实验。此外，通过体外皮肤渗透研究考察了药物从LC制剂中的皮肤渗透情况。结果表明，虽然释放曲线受MGE浓度变化的影响，但更受包载药物理化性质变化的显著影响。LC制剂口服和外用给药后的药物吸收受MGE浓度的显著影响。形成LC的脂质浓度和包载药物的理化性质是LC制剂在各种药物应用中表现良好的关键因素。目前的结果可以使研究人员操控旨在改善药物口服吸收和皮肤渗透的LC制剂方法。
