Abstract：
Eudragit S100-coated bile salt-containing liposomes were prepared and optimized by experimenting with different variables, including bile salt type and concentration, and the method of incorporation into liposomes using a model hydrophilic compound, 5-aminosalicylic acid (5-ASA). After optimizing the formulation, cellular uptake, and animal pharmacokinetic experiments were performed. The inclusion of sodium glycocholate (SG) into liposomes decreased liposome particle size and entrapment efficiency significantly but had no effect on zeta potential. The method of incorporating SG into the lipid or aqueous phase of the liposome did not notably impact the characteristics of the liposomes but the hydration media had a substantial effect on the entrapment efficiency of 5-ASA. In vitro drug release in different fluids simulating distinct gastrointestinal tract sections, indicated pH-dependent disintegration of the coating layer of coated SG-containing liposomes. The majority of the drug was retained when subjected to simulated gastric fluid (SGF) and fed-state simulated intestinal fluid (FeSSIF) (≈ 37% release after 2 h in SGF pH 1.2, followed by 3 h in FeSSIF pH 5). The remaining drug was subsequently released in phosphate-buffered saline pH 7.4 (≈ 85% release within 24 h). Increasing SG concentration in the liposomes decreased the amount of drug released in FeSSIF. Similar results were observed when SG was replaced with sodium taurocholate. Cellular uptake studies in Caco-2 cells demonstrated that all liposomal formulations (conventional liposomes, bile salt-containing liposomes, and coated bile salt-containing liposomes) have shown to be equally effective at increasing the cellular uptake compared to free fluorescein solution. In the pharmacokinetic study, coated bile salt-containing liposomes showed a lower Cmax and prolonged residence in the gastrointestinal tract in comparison to conventional liposomes. Taken together, these findings suggest that the polymer-coated bile salt-containing liposomes have the potential to serve as a drug delivery system targeted at the colon.
摘要：
通过不同变量的实验，制备了EudragitS100包被的胆盐脂质体并进行了优化，包括胆盐类型和浓度，以及使用模型亲水化合物掺入脂质体的方法，5-氨基水杨酸(5-ASA)。优化配方后，细胞摄取，并进行了动物药代动力学实验。将甘氨胆酸钠（SG）包含在脂质体中显着降低了脂质体的粒径和包封率，但对ζ电位没有影响。将SG掺入脂质体的脂质相或水相中的方法没有显著影响脂质体的特性,但是水合介质对5-ASA的包封效率具有显著影响。模拟不同胃肠道切片的不同液体中的体外药物释放，显示了包衣的含SG脂质体的包衣层的pH依赖性崩解。当经受模拟胃液（SGF）和进食状态模拟肠液（FeSSIF）时，大部分药物被保留（在pH1.2的SGF中2小时后约37％释放，然后在pH5的FeSSIF中3小时）。剩余的药物随后在pH7.4的磷酸盐缓冲盐水中释放(在24小时内释放约85%)。脂质体中SG浓度的增加降低了FeSSIF中释放的药物量。当用牛磺胆酸钠代替SG时,观察到类似的结果。Caco-2细胞的细胞摄取研究表明，所有脂质体制剂（常规脂质体，含胆汁盐的脂质体，和含胆汁盐的包被脂质体）与游离荧光素溶液相比，在增加细胞摄取方面表现出同样有效。在药代动力学研究中，与常规脂质体相比,含有胆盐的包被脂质体显示出较低的Cmax和在胃肠道中的停留时间延长.一起来看,这些发现表明,聚合物包被的含胆汁盐的脂质体具有作为靶向结肠的药物递送系统的潜力.
