Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Horus University, New Damietta, Egypt.
AAPS PharmSciTech. 2024 Nov 5;25(8):264. doi: 10.1208/s12249-024-02962-z.
Rivaroxaban is an anticoagulant for avoidance and therapy of thromboembolic disorders. Unfortunately, oral bioavailability of rivaroxaban is compromised with dose increments. Accordingly, the aim was to test nano-vesicular lipid systems for improved oral anticoagulation activity of rivaroxaban. Rivaroxaban loaded niosomes, bilosomes and spanlastic formulations were prepared. The prepared systems were assessed in terms of particle size, zeta potential, transition electron microscopic features (TEM), entrapment efficiency, in-vitro drug release, and in-vivo anticoagulation performance in rats. The prepared vesicular systems exposed spherical negatively charged vesicles with mean particle size values between 136.6 nm to 387.9 nm depending on the composition. Rivaroxaban was efficiently entrapped in the vesicular systems with entrapment efficiency values ranging from 92.4% to 94.0%. Rivaroxaban underwent sustained release from the fabricated vesicular systems. The in vivo performance of the tested preparation revealed significant enhancement of the anticoagulation parameters. This was manifested from the prolonged clotting time, and prothrombin time. Moreover, the cut tails of the examined rats receiving the formulated nano-systems exposed a lengthy tail bleeding time compared to those receiving the un-processed rivaroxaban aqueous dispersion. In Conclusion, niosomes, bilosomes and spanlastic nano-dispersions have a potential to overwhelm the oral anticoagulation efficiency of rivaroxaban with spanlastic ranked as best.
利伐沙班是一种用于预防和治疗血栓栓塞性疾病的抗凝剂。不幸的是，利伐沙班的口服生物利用度会随着剂量的增加而降低。因此，本研究旨在测试纳米囊泡脂质系统，以提高利伐沙班的口服抗凝活性。制备了载利伐沙班的非离子型脂质体、双分子层囊泡和变形脂质体。从粒径、Zeta 电位、透射电子显微镜（TEM）特征、包封效率、体外药物释放以及大鼠体内抗凝性能等方面对制备的系统进行了评价。所制备的囊泡系统暴露的是具有平均粒径在 136.6nm 到 387.9nm 之间的球形带负电荷的囊泡，具体取决于组成。利伐沙班被高效包封在囊泡系统中，包封效率值在 92.4%到 94.0%之间。利伐沙班从所制备的囊泡系统中进行了持续释放。体内性能研究表明，所测试的制剂能显著增强抗凝参数。这表现在凝血时间和凝血酶原时间的延长。此外，接受所制备的纳米系统的实验大鼠的尾巴被切断，与接受未经处理的利伐沙班水混悬液的大鼠相比，尾巴出血时间明显延长。总之，非离子型脂质体、双分子层囊泡和变形脂质体纳米分散体具有提高利伐沙班口服抗凝效率的潜力，其中变形脂质体的效果最佳。
