Abstract：
In this article, we described a novel antituberculosis imidazotetrazine derivative designed in fucoidan-coated liposomes to reduce its cytotoxicity and investigate its mucoadhesive properties. Firstly, fucoidan extracted from Ascophyllum nodosum was used for additional stabilization of liposomal suspensions and to give it mucoadhesive properties. PEG-600 and/or Tween-80 were used to increase the shelf life of liposomal suspension. The ratio of the fucoidan: lipids 1:2 was found to be the optimum that produces stable fucoidan-coated liposomes. The particle size of the optimum formulation was 336.3 ± 5.4, the PDI was 0.33, and the zeta potential was -39.6. This size and the practical spherical shape of the particles were confirmed by atomic force microscopy. In addition, the in vitro release profiles from uncoated and fucoidan-coated liposomes revealed significant and faster release compared to free antituberculosis agent. Using the MTT assay test, the fucoidan-coated liposomes exhibited fourteen times lower cytotoxicity (IC50 7.14 ± 0.91 µg/ml) than the free drug (IC50 0.49 ± 0.06). Moreover, the mucoadhesive capabilities of these liposomal formulations were also confirmed using snail mucin, which highlighting their potential use as an effective delivery system for antituberculosis therapy, with notable improvements in dissolution rate and reduced cytotoxicity.
摘要：
在这篇文章中,我们描述了一种在岩藻依聚糖包被的脂质体中设计的新型抗结核药咪唑四嗪衍生物，以降低其细胞毒性并研究其粘膜粘附特性。首先,从结鞘藻提取的岩藻依聚糖用于脂质体悬浮液的额外稳定并赋予其粘膜粘附特性。PEG-600和/或Tween-80用于增加脂质体悬浮液的保质期。发现岩藻依聚糖:脂质的比例为1:2是产生稳定的岩藻依聚糖包被的脂质体的最佳值。最佳配方的粒径为336.3±5.4，PDI为0.33，ζ电位为-39.6。通过原子力显微镜确认了颗粒的这种尺寸和实际球形。此外,与游离抗结核药相比，未包衣和岩藻依聚糖包衣脂质体的体外释放曲线显示出显着和更快的释放。使用MTT化验测试，岩藻依聚糖包被的脂质体的细胞毒性(IC50为7.14±0.91µg/ml)比游离药物(IC50为0.49±0.06)低14倍.此外，使用蜗牛粘蛋白也证实了这些脂质体制剂的粘膜粘附能力，突出了它们作为抗结核治疗有效输送系统的潜在用途，具有显著改善的溶解速率和降低的细胞毒性。
