Given that literature data may give inconsistent results on the effect of a drug on lipid membrane properties, this work aims to investigate the impact of the liposome composition and experimental protocol design on glucocorticoids (GRs: cortisol, cortisone, fludrocortisone acetate, methylprednisolone, prednisolone and prednisone)-modulating membrane fluidity and permeability. GRs-loaded liposomes consisting of dipalmitoylphosphatidylcholine (DPPC) and cholesterol (CHOL) were prepared by reverse phase evaporation technique (REV) at DPPC:CHOL:GR molar ratios of 100:100:2.5, and 100:100:10. The formulations were characterized for their size and homogeneity, encapsulation efficiency and loading rates of GRs, incorporation rates and loading rates of DPPC and CHOL. Changes in DPPC membrane fluidity (CHOL% 0, 10, 20, 30 and 100) after exposure to methylprednisolone were monitored by using 5- and 16-doxyl stearic acids (DSA) as spin probes. For permeability studies, the above-mentioned GRs-loaded liposomes and the preformed liposomes exposed to GRs (2.5 mol%) were compared for the leakage of an encapsulated fluorescent dye, sulforhodamine B (SRB), at 37 °C in buffer (pH 7.5) containing NaCl. The SRB release kinetics were analyzed by the Higuchi model for two release phases (from 0 to 10 h, and from 10 to 48 h). All formulations exhibited a monodispersed size distribution of liposomes with a mean particle value close to 0.4 μm, also the DPPC and CHOL were highly incorporated (>95%). High loading rate values of DPPC and CHOL were also obtained. Except for fludrocortisone acetate (51%) and prednisolone (77%), high loading rate values of GRs were obtained (>81%). Fluidity and permeability studies showed that the GR concentration, CHOL content, experimental protocol design including the period of incubation represent critical parameters to be considered in analyzing the effect of drugs on the membrane properties.

鉴于文献数据可能无法就药物对脂质膜特性的作用产生不一致的结果，因此本研究旨在研究脂质体组成和实验方案设计对糖皮质激素的影响（GRs：皮质醇，可的松，醋酸氟可的松，甲基强的松龙，泼尼松龙和泼尼松）调节膜的流动性和渗透性。通过反相蒸发技术（REV）以DPPC：CHOL：GR摩尔比为100：100：2.5和100：100：10制备由二棕榈酰磷脂酰胆碱（DPPC）和胆固醇（CHOL）组成的GRs脂质体。对制剂的大小和均一性，GRs的包封效率和上样率，DPPC和CHOL的掺入率和上样率进行了表征。DPPC膜流动性的变化（CHOL％0、10、20，暴露于甲基强的松龙中的30和100）通过使用5-和16-羟基硬脂酸（DSA）作为自旋探针进行监测。为了进行渗透性研究，比较了上述负载GRs的脂质体和暴露于GRs（2.5 mol％）的预制脂质体在37°C的缓冲液（pH 7.5）中封装的荧光染料磺基若丹明B（SRB）的泄漏情况。 ）含有NaCl。通过Higuchi模型分析了两个释放阶段（从0到10小时，从10到48小时）的SRB释放动力学。所有制剂均表现出脂质体的单分散尺寸分布，平均粒径接近0.4μm，并且高度掺入了DPPC和CHOL（> 95％）。还获得了DPPC和CHOL的高加载率值。除醋酸氟可的松（51％）和泼尼松龙（77％）以外，均获得了较高的GRs负载率值（> 81％）。流动性和渗透性研究表明，GR浓度，CHOL含量，实验方案设计（包括孵育时间）是分析药物对膜特性影响时要考虑的关键参数。