Tizanidine hydrochloride (TZN) is one of the most effective centrally acting skeletal muscle relaxants. The objective of this study is to prepare TZN-loaded proniosomes (TZN-PN) aiming at enhanced oral delivery and therapeutic activity. TZN-PN were prepared by coacervation phase separation method. The developed vesicles were characterized via entrapment efficiency percentage (EE%), vesicular size (VS), and zeta potential (ZP). A 2³ full factorial design was employed to attain an optimized TZN-PN formulation. The optimized TZN-PN were further characterized via in vitro release study and transmission electron microscopy (TEM). In vivo rotarod test was employed for determination of the muscle relaxant activities of rats and levels of GABA and EAAT2 were detected. The developed TZN-PN exhibited relatively high EE% (75.78–85.45%), a VS ranging between (348–559 nm), and a ZP (−26.47 to −59.64). In vitro release profiles revealed sustained release of TZN from the optimized TZN-PN, compared to free drug up to 24 h. In vivo rotarod study revealed that the elevation in coordination was in the following order: normal control < free TZN < market product < TZN-PN (F6). Moreover, the optimized TZN-PN exhibited significant elevated coordination activity by 39% and 26% compared to control group and market product group, respectively. This was accompanied with an elevation in both GABA and EAAT2 serum levels. Thus, it could be concluded that encapsulation of TZN in the provesicular nanosystem proniosomes has enhanced the anti-nociceptive effect of the drug and consequently its therapeutic activity.

Graphical abstract

中文翻译：

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采用 23 全析因设计改善口服给药和治疗活性的盐酸替扎尼定负载前体系统的配方

盐酸替扎尼定 (TZN) 是最有效的中枢作用骨骼肌松弛剂之一。本研究的目的是制备载有 TZN 的前核小体 (TZN-PN)，旨在增强口服给药和治疗活性。TZN-PN 采用凝聚相分离法制备。开发的囊泡通过包封效率百分比 (EE%)、囊泡大小 (VS) 和 zeta 电位 (ZP) 进行表征。一个 2 ³采用全因子设计来获得优化的 TZN-PN 配方。通过体外释放研究和透射电子显微镜 (TEM) 进一步表征优化的 TZN-PN。采用体内转棒试验测定大鼠肌松活性，检测GABA和EAAT2水平。开发的 TZN-PN 表现出相对较高的 EE% (75.78–85.45%)，VS 介于 (348–559 nm) 之间，ZP (-26.47 至 -59.64)。体外释放曲线显示，与游离药物相比，TZN 从优化的 TZN-PN 中持续释放长达 24 小时。体内旋转棒研究表明，协调性升高的顺序如下：正常对照 < 游离 TZN < 市场产品 < TZN-PN (F6)。而且，与对照组和市场产品组相比，优化后的 TZN-PN 的协调活性显着提高了 39% 和 26%。这伴随着 GABA 和 EAAT2 血清水平的升高。因此，可以得出结论，将 TZN 包裹在 prosicular 纳米系统 proniosomes 中增强了药物的抗伤害作用，从而增强了其治疗活性。

图形概要