Cámara Candelaria Ines, Crosio Matías Ariel, Juarez Ana Valeria, Wilke Natalia
Departamento de Fisicoquímica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina.
Instituto de Investigaciones en Fisicoquímica de Córdoba (INFIQC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba X5000HUA, Argentina.
Pharmaceutics. 2023 Mar 4;15(3):844. doi: 10.3390/pharmaceutics15030844.
Dexamethasone (Dex) and Dexamethasone phosphate (Dex-P) are synthetic glucocorticoids with high anti-inflammatory and immunosuppressive actions that gained visibility because they reduce the mortality in critical patients with COVID-19 connected to assisted breathing. They have been widely used for the treatment of several diseases and in patients under chronic treatments, thus, it is important to understand their interaction with membranes, the first barrier when these drugs get into the body. Here, the effect of Dex and Dex-P on dimyiristoylphophatidylcholine (DMPC) membranes were studied using Langmuir films and vesicles. Our results indicate that the presence of Dex in DMPC monolayers makes them more compressible and less reflective, induces the appearance of aggregates, and suppresses the Liquid Expanded/Liquid Condensed (LE/LC) phase transition. The phosphorylated drug, Dex-P, also induces the formation of aggregates in DMPC/Dex-P films, but without disturbing the LE/LC phase transition and reflectivity. Insertion experiments demonstrate that Dex induces larger changes in surface pressure than Dex-P, due to its higher hydrophobic character. Both drugs can penetrate membranes at high lipid packings. Vesicle shape fluctuation analysis shows that Dex-P adsorption on GUVs of DMPC decreases membrane deformability. In conclusion, both drugs can penetrate and alter the mechanical properties of DMPC membranes.
地塞米松（Dex）和地塞米松磷酸酯（Dex-P）是具有高抗炎和免疫抑制作用的合成糖皮质激素，因其降低了与辅助呼吸相关的COVID-19重症患者的死亡率而受到关注。它们已被广泛用于治疗多种疾病以及慢性治疗患者，因此，了解它们与细胞膜（这些药物进入人体时的第一道屏障）的相互作用非常重要。在此，使用朗缪尔膜和囊泡研究了Dex和Dex-P对二肉豆蔻酰磷脂酰胆碱（DMPC）膜的影响。我们的结果表明，DMPC单层中Dex的存在使其更易压缩且反射性更低，诱导聚集体的出现，并抑制液晶态/液晶态凝聚（LE/LC）相变。磷酸化药物Dex-P也会在DMPC/Dex-P膜中诱导聚集体的形成，但不会干扰LE/LC相变和反射率。插入实验表明，由于Dex具有更高的疏水性，其引起的表面压力变化比Dex-P更大。两种药物在高脂质堆积情况下都能穿透细胞膜。囊泡形状波动分析表明，Dex-P吸附在DMPC的巨型单层囊泡（GUV）上会降低膜的可变形性。总之，两种药物都能穿透并改变DMPC膜的力学性质。
