Department of Chemistry, Lancaster University, Lancaster, LA1 4YB, United Kingdom.
Materials Science Institute, Lancaster University, Lancaster, LA1 4YB, United Kingdom.
Chempluschem. 2021 Nov;86(11):1517-1523. doi: 10.1002/cplu.202100385. Epub 2021 Nov 2.
Drug interactions with phospholipid bilayers underpin their behaviour in cell membranes and in liposomal delivery formulations. Liposomal drug delivery in ocular medicine can overcome the physical barriers of the eye and better enable the active molecule to reach its target. Here, Raman and F solid-state NMR spectroscopy are used to characterise the interactions of two ocular corticosteroid drugs, difluprednate (DFP) and fluorometholone (FML), with multilamellar vesicles of phosphatidylcholine (PC). P NMR confirms that the lipid bilayer tolerates a high drug concentration (a drug: lipid molar ratio of 1 : 10). The F NMR spectra of the drugs in lipid bilayers reveal that FML and DFP have different average orientations within the lipid bilayer. Raman spectra of dried lipid films reveal that PC separates from DFP but not from FML, the less lipophilic of the two drugs. This combined approach will assist the design of, and inform the development of, improved liposomal preparations.
药物与磷脂双层的相互作用是它们在细胞膜和脂质体递药配方中行为的基础。眼用脂质体递药可以克服眼部的物理屏障，使活性分子更好地到达靶标。在这里，拉曼和 F 固态 NMR 光谱用于表征两种眼部皮质类固醇药物二氟泼尼龙（DFP）和氟米龙（FML）与磷脂酰胆碱（PC）的多层囊泡的相互作用。 13 C NMR 证实脂质双层可以耐受高药物浓度（药物：脂质摩尔比为 1:10）。脂质双层中药物的 19 F NMR 光谱表明，FML 和 DFP 在脂质双层内具有不同的平均取向。干燥脂质膜的拉曼光谱表明，PC 与 DFP 分离，但与两种药物中疏水性较小的 FML 不分离。这种综合方法将有助于改进脂质体制剂的设计，并为其开发提供信息。
