摘要
目的优化黄芪甲苷脂质体处方及制备工艺,进行制剂学评价,并考察其对大鼠缺血性脑卒中的治疗效果。方法以粒径、多分散系数(PDI)、电位和包封率为指标,单因素考察黄芪甲苷脂质体处方及工艺,并对黄芪甲苷脂质体进行质量评价。采用线栓法行大脑中动脉栓塞手术,建立缺血性脑卒中大鼠模型。将大鼠分为假手术组、模型组、黄芪甲苷组、黄芪甲苷脂质体组,观察大鼠神经行为学变化,并检测脑组织梗死比率、病理变化等指标。结果最优处方及工艺为蛋黄卵磷脂8 mg·mL-1,膜材比10∶3,投药量1 mg,水化温度48℃,超声功率300 W,超声时间8 min。制备的黄芪甲苷脂质体平均粒径为(185.97±2.55)nm,PDI为0.258±0.012,zeta电位为(-19.91±0.52)mV,包封率为94.58%±0.67%,4℃储存7 d粒径变化小于5 nm,4 h药物累积释放率为39%,表现出缓释效果。药效实验中,黄芪甲苷脂质体能明显降低大鼠神经行为缺陷评分及脑组织梗死比率,并减少病理变化。结论黄芪甲苷脂质体粒径较小,包封率高,具有良好的储存稳定性和缓释特性,对缺血性脑卒中具有优异的治疗效果。
Objective To optimize the formulation and preparation process of astragaloside IV liposome,conduct the pharmaceutical evaluation of the liposome,and investigate its therapeutic effect on ischemic stroke in rats.Methods Particle size,polydispersity index(PDI),zeta potential,and encapsulation efficiency were used as investigative factors.Based on above,the formulation and process of astragaloside IV liposome were optimized by single factor analysis.The quality of astragaloside IV liposome was evaluated.The middle cerebral artery embolization surgery was performed using the suture method to establish an ischemic stroke rat model.The mice were divided into sham surgery group,model group,astragaloside IV group,and astragaloside IV liposome group.The neurobehavioral changes of the rats,and detect indicators such as brain tissue infarction rate and pathological changes were observed.Results The optimal process parameters were as follows:the mass concentration of egg yolk lecithin was 8 mg·mL^(-1),the ratio of membrane to material was 10∶3,the dosage of astragaloside IV was 1 mg,hydration temperature was 48℃,ultrasound power was 300 W,and ultrasound time was 8 min.The average particle size,PDI,zeta potential,encapsulation efficiency of the prepared astragaloside IV liposome was(185.97±2.55)nm,0.258±0.012,(-19.91±0.52)mV,and 94.58%±0.67%,respectively.The particle size change of astragaloside IV liposome was less than 5 nm at 4℃within 7 days.Furthermore,the cumulative release of astragaloside IV in astragaloside IV liposome was 39%at 4 h,demonstrating the sustained release effect.In pharmacological experiments,astragaloside IV liposome could significantly reduce the scores of neurobehavioral deficits and the incidence of brain tissue infarction in rats,as well as reduce pathological changes.Conclusion Astragaloside IV liposome present small particle size,high encapsulation efficiency,good storage stability,sustained-release properties,and excellent therapeutic effects on ischemic stroke.
作者
杨露
李秋霞
马理园
尹少平
罗开沛
YANG Lu;LI Qiuxia;MA Liyuan;YIN Shaoping;LUO Kaipei(Institute of Traditional Chinese Medicine Innovation,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;Meishan Hospital of Traditional Chinese Medicine Affiliated to Chengdu University of Traditional Chinese Medicine,Meishan 620032,China;State Key Laboratory of Southwestern Chinese Medicine Resources,College of Pharmacy,Chengdu University of Chinese Medicine,Chengdu 611137,China;School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China)
出处
《药学研究》
CAS
2024年第9期833-839,共7页
Journal of Pharmaceutical Research
基金
国家自然科学基金(No.82304880、82204633)
四川省自然科学基金(No.2023NSFSC1782)。
关键词
黄芪甲苷
脂质体
制备工艺
稳定性
体外释放
缺血性脑卒中
药效学
Astragaloside IV
Liposome
Preparation process
Stability
In vitro release
Ischemic stroke
Pharmacodynamics
