Zhang Wei, Wang Xiaoyu, Zhang Min, Xu Min, Tang Wenyan, Zhang Yi, Lu Lei, Gao Jing, Gao Shen
Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School, Shanghai 200433, China
Department of Pharmacy of the Second Military Medical University Changhai Hospital, Shanghai 200433, P.R. China
Curr Drug Deliv. 2017 Sep 6;14(6):867-874. doi: 10.2174/1567201814666161109121151.
Nasal delivery of 20 (R) -ginsenoside Rg3 (Rg3) has a short-lived anti-fatigue effect owing to rapid clearance by nasal cilia. Thus, in order to extend the residence time of Rg3 in the nasal cavity, a new drug delivery system is needed.
Chitosan microspheres loaded with Rg3 were prepared using a multi-step emulsification method and were characterized in vitro and in vivo.
The microspheres had a spherical shape with a mean diameter of 44.9±12.6 08m. The drugloading ratio was 10.25±0.08%, and the encapsulation ratio was 30.61±1.46%. Our in vitro mucoadhesion experiment demonstrated that 70.35±1.79% of the microspheres adhered to the nasal mucosa. The in vitro release study revealed that 31.1% of the Rg3 was released from the microspheres in the first 10 min. Release slowed, with 88.64% of the Rg3 released within 6 h. The pharmacodynamics study demonstrated that the weight-bearing swimming time of mice increased significantly from 432±89 s to 486±96 s after administration of Rg3 microspheres compared with the Rg3 water solution. Blood lactic acid and serum urea nitrogen significantly decreased in the group administered microspheres compared to the water solution group (p<0.05). Hepatic glycogen and lactate dehydrogenase increased significantly in the group administered microspheres compared to the water solution group (p<0.01).
20 (R) -ginsenoside Rg3 entrapped in chitosan microspheres may have a beneficial effect against fatigue by increasing the residence time of Rg3 in the nasal cavity and enhancing absorption by the nasal mucosa.
由于鼻腔纤毛的快速清除作用,经鼻腔给药的20(R)-人参皂苷Rg3(Rg3)具有短暂的抗疲劳效果。因此,为了延长Rg3在鼻腔中的停留时间,需要一种新的药物递送系统。
采用多步乳化法制备了负载Rg3的壳聚糖微球,并进行了体外和体内表征。
微球呈球形,平均直径为44.9±12.6μm。载药率为10.25±0.08%,包封率为30.61±1.46%。我们的体外黏膜黏附实验表明,70.35±1.79%的微球黏附于鼻黏膜。体外释放研究显示,Rg3在最初10分钟内从微球中释放出31.1%。释放速度减慢,6小时内88.64%的Rg3被释放。药效学研究表明,与Rg3水溶液相比,给予Rg3微球后小鼠的负重游泳时间从432±89秒显著增加到486±96秒。与水溶液组相比,微球给药组的血乳酸和血清尿素氮显著降低(p<0.05)。与水溶液组相比,微球给药组的肝糖原和乳酸脱氢酶显著增加(p<0.01)。
包裹在壳聚糖微球中的20(R)-人参皂苷Rg3可能通过增加Rg3在鼻腔中的停留时间并增强鼻黏膜吸收而对疲劳产生有益作用。