摘要
目的制备金丝桃苷磷脂复合物(hyperosidephospholipidscomplex,Hyp-PC)介孔二氧化硅纳米粒(Hyp-PC mesoporous silica nanoparticles,Hyp-PC-MSN),考察口服药动学行为。方法以复合率为指标,单因素实验结合Box-Behnken设计-效应面法优化Hyp-PC处方。X射线粉末衍射(X-ray powder diffraction,XRPD)对Hyp-PC进行晶型分析,并测定Hyp-PC的油水分配系数。溶剂挥发法制备Hyp-PC-MSN,扫描电子显微镜观察Hyp-PC-MSN微观形态,并与Hyp-PC比较Hyp-PC-MSN体外溶出情况。SD大鼠分为金丝桃苷组、Hyp-PC组和Hyp-PC-MSN组,测定大鼠血浆中金丝桃苷质量浓度,计算Hyp-PC和Hyp-PC-MSN主要药动学参数及相对口服吸收生物利用度。结果Hyp-PC最佳处方的复合率接近100%,金丝桃苷在Hyp-PC中以无定型状态存在,油水分配系数明显增大。Hyp-PC-MSN外观形态呈球形,包封率为(93.17±0.85)%,载药量为(7.54±0.33)%,粒径为(163.87±6.15)nm,PDI值为0.108±0.009,ζ电位为(-0.28±0.05)m V。Hyp-PC-MSN明显提高了释药速率和累积释放度。药动学结果显示,Hyp-PC-MSN的达峰时间(tmax)显著性提前,半衰期(t1/2)延长至(4.56±0.82)h,达峰浓度(Cmax)提高至(1462.62±163.94)ng/mL,相对口服生物利用度提高至3.47倍。结论Hyp-PC-MSN可提高金丝桃苷体外溶出速率、累积溶出度及口服吸收生物利用度。
Objective To prepare hyperoside phospholipids complex(Hyp-PC)mesoporous silica nanoparticles(Hyp-PC-MSN),and study oral pharmacokinetics behavior.Methods Taking the recombination rate as index,single factor experiment combined with Box-Behnken design-response surface methodology to optimize the formulation of Hyp-PC.Crystalline form of Hyp-PC was analyzed by X-ray powder diffraction(XRPD).Oil-water partition coefficient of Hyp-PC was determined.Solvent evaporation was used to prepare Hyp-PC-MSN.Microscopic appearance of Hyp-PC-MSN was observed by scanning electron microscope(SEM),and its dissolution in vitro was compared to Hyp-PC.SD rats were divided into hyperoside suspension group,Hyp-PC group and Hyp-PC-MSN group,hyperoside concentration in plasma was determined,and main pharmacokinetic parameters and relative oral bioavailability of Hyp-PC and Hyp-PC-MSN were calculated.Results Recombination rate of optimized formulations of Hyp-PC was close to 100%.Hyperoside was an amorphous substance in Hyp-PC and the oil-water partition coefficient was enhanced greatly.Microscopic appearance of Hyp-PC-MSN was spherical in shape.Average envelopment efficiency was(93.17±0.85)%,drug loading was(7.54±0.33)%,particle size was(163.87±6.15)nm,PDI value was 0.108±0.009 and ζ potential was(-0.28±0.05)mV.Drug release rate and cumulative release rate in vitro was greatly promoted.Pharmacokinetics results showed that tmax of Hyp-PC-MSN was advanced significantly,t1/2 was prolonged to(4.56±0.82)h,Cmax was increased to(1462.62±163.94)ng/mL and oral bioavailability was enhanced to 3.47 times.Conclusion Hyp-PC-MSN could increase dissolution rate,cumulative dissolution rate in vitro and the oral bioavailability of hyperoside.
作者
李伟宏
郑伟
王风云
隋海娟
LI Wei-hong;ZHENG Wei;WANG Feng-yun;SUI Hai-juan(Henan Vocational College of Applied Technology,Zhengzhou 450042,China;Jinzhou Medical University,Jinzhou 121001,China)
出处
《中草药》
CAS
CSCD
北大核心
2023年第13期4157-4167,共11页
Chinese Traditional and Herbal Drugs
基金
河南省高等学校重点科研项目计划(23B320013)
妇科肿瘤科研创新团队(2021-TD-02)
河南应用技术职业学院骨干教师(2020-GGJS-Y008)。
关键词
金丝桃苷
磷脂复合物
油水分配系数
介孔二氧化硅纳米粒
溶出速率
累积溶出度
生物利用度
hyperoside
phospholipids complex
oil-water partition coefficient
mesoporous silica nanoparticles
dissolution rate
cumulative dissolution rate
bioavailability
