Abstract Bilosomes were developed in order to investigate their efficacy as nanocarriers for transdermal delivery of Tizanidine HCl (TZN), a skeletal muscle relaxant with low oral bioavailability. Full factorial experimental design consisting of 27 combinations was generated to study the effects of surfactant type, surfactant-to-cholesterol ratio and the amount of bile salt on the entrapment efficiency (EE), the vesicle size (VS) and in vitro dissolution of the TZN-loaded bilosomes. The permeation through the stratum cornea was optimized with the vertical diffusion assembly using excised rat skin. The permeation parameters of the selected bilosomes were compared to the unformulated drug and it was shown that TZN-B24 exhibited the highest enhancement ratio (ER = 8.8).The optimal formula (TZN-B24) consisting of span 60 in a ratio with cholesterol of 1:1 and 20 mg of bile salt was obtained by employing the desirability function of Design-Expert® software. The mathematical model used for the optimization was validated by comparing the predicted values of the EE (82.3%) and the VS (165.8 nm) with the experimental values of EE = 84.42% and of VS = 161.95 nm. TZN-B24 displayed high zeta potential which contributed to its good stability. It was evident from the results of this study that incorporating TZN in bilosomes improved significantly its permeation through the skin barrier and thus bilosomes can offer a potential nanoplatform using the transdermal route to improve the bioavailability of the drug.

中文翻译：

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Bilosomes 作为纳米载体用于盐酸替扎尼定透皮给药的评价：体外和体外优化

摘要 Bilosomes 的开发是为了研究它们作为纳米载体用于透皮递送盐酸替扎尼定 (TZN) 的功效，Tizanidine HCl (TZN) 是一种口服生物利用度低的骨骼肌松弛剂。生成由 27 种组合组成的全因子实验设计，以研究表面活性剂类型、表面活性剂与胆固醇的比例和胆汁盐量对包封率 (EE)、囊泡大小 (VS) 和体外溶出度的影响。装载 TZN 的双糖体。通过使用离体大鼠皮肤的垂直扩散组件优化通过角膜层的渗透。将所选胆囊体的渗透参数与未配制的药物进行比较，结果表明 TZN-B24 表现出最高的增强率 (ER = 8.8)。使用Design-Expert®软件的合意性函数，得到了最佳配方（TZN-B24），其中span 60与胆固醇的比例为1:1，胆盐为20 mg。通过将 EE (82.3%) 和 VS (165.8 nm) 的预测值与 EE = 84.42% 和 VS = 161.95 nm 的实验值进行比较，验证了用于优化的数学模型。TZN-B24 显示出高 zeta 电位，这有助于其良好的稳定性。从这项研究的结果中可以明显看出，将 TZN 加入到胆囊体中可显着提高其通过皮肤屏障的渗透性，因此胆囊体可以提供一个潜在的纳米平台，使用经皮途径来提高药物的生物利用度。通过将 EE (82.3%) 和 VS (165.8 nm) 的预测值与 EE = 84.42% 和 VS = 161.95 nm 的实验值进行比较，验证了用于优化的数学模型。TZN-B24 显示出高 zeta 电位，这有助于其良好的稳定性。从这项研究的结果中可以明显看出，将 TZN 加入到胆囊体中可显着提高其通过皮肤屏障的渗透性，因此胆囊体可以提供一个潜在的纳米平台，使用经皮途径来提高药物的生物利用度。通过将 EE (82.3%) 和 VS (165.8 nm) 的预测值与 EE = 84.42% 和 VS = 161.95 nm 的实验值进行比较，验证了用于优化的数学模型。TZN-B24 显示出高 zeta 电位，这有助于其良好的稳定性。从这项研究的结果中可以明显看出，将 TZN 加入到胆囊体中可显着提高其通过皮肤屏障的渗透性，因此胆囊体可以提供一个潜在的纳米平台，使用经皮途径来提高药物的生物利用度。