Hägerbäumer Pia, Gräbitz-Bräuer Friederike, Annegarn Marco, Dargel Carina, Stank Tim Julian, Bizien Thomas, Hellweg Thomas
Physical and Biophysical Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany.
Institute of Physical Chemistry, University of Münster, Corrensstr. 28/30, 48149 Münster, Germany.
Pharmaceutics. 2023 Jan 22;15(2):379. doi: 10.3390/pharmaceutics15020379.
In this study, the interplay among the phospholipid 1,2-dimyristoyl--glycero-3-phosphocholine (DMPC) as a model membrane, the nonsteroidal anti-inflammatory drug naproxen, and the saponin β-aescin are investigated. The naproxen amount was fixed to 10 mol%, and the saponin amount varies from 0.0 to 1.0 mol%. Both substances are common ingredients in pharmaceutics; therefore, it is important to obtain deeper knowledge of their impact on lipid membranes. The size and properties of the DMPC model membrane upon naproxen and aescin addition were characterized with differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SAXS, WAXS), and photon correlation spectroscopy (PCS) in a temperature-dependent study. The interaction of all substances was dependent on the lipid phase state, which itself depends on the lipid's main phase transition temperature Tm. The incorporation of naproxen and aescin distorted the lipid membrane structure and lowers Tm. Below Tm, the DMPC-naproxen-aescin mixtures showed a vesicle structure, and the insertion of naproxen and aescin influenced neither the lipid chain-chain correlation distance nor the membrane thickness. Above Tm, the insertion of both molecules instead induced the formation of correlated bilayers and a decrease in the chain-chain correlation distance. The presented data clearly confirm the interaction of naproxen and aescin with DMPC model membranes. Moreover, the incorporation of both additives into the model membranes is evidenced.
在本研究中,对作为模型膜的磷脂1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱(DMPC)、非甾体抗炎药萘普生和皂苷七叶皂苷之间的相互作用进行了研究。萘普生的量固定为10摩尔%,皂苷的量在0.0至1.0摩尔%之间变化。这两种物质都是药物制剂中的常见成分;因此,深入了解它们对脂质膜的影响非常重要。在一项温度依赖性研究中,采用差示扫描量热法(DSC)、小角和广角X射线散射(SAXS、WAXS)以及光子相关光谱法(PCS)对添加萘普生和七叶皂苷后的DMPC模型膜的大小和性质进行了表征。所有物质之间的相互作用取决于脂质相态,而脂质相态本身又取决于脂质的主要相变温度Tm。萘普生和七叶皂苷的掺入扭曲了脂质膜结构并降低了Tm。在Tm以下,DMPC-萘普生-七叶皂苷混合物呈现囊泡结构,萘普生和七叶皂苷的插入既不影响脂质链-链相关距离,也不影响膜厚度。在Tm以上,两种分子的插入反而诱导了相关双层的形成并使链-链相关距离减小。所呈现的数据清楚地证实了萘普生和七叶皂苷与DMPC模型膜之间的相互作用。此外,还证明了两种添加剂都掺入到了模型膜中。