摘要
目的制备二硬脂酰磷脂酰乙醇胺-聚乙二醇2000(DSPE-mPEG2000)修饰荷叶碱脂质体,并考察其体内药动学。方法薄膜超声法制备脂质体。以磷脂酰胆碱与胆固醇比例、脂药比、DSPE-mPEG2000用量、水化温度、超声时间为影响因素,单因素试验优化处方,测定包封率、载药量、粒径、PDI、Zeta电位、体外释药。18只大鼠随机分为3组,分别灌胃给予荷叶碱原料药、不含DSPE-mPEG2000荷叶碱脂质体、DSPE-mPEG2000修饰荷叶碱脂质体的0.5%CMC-Na混悬液(20 mg/kg),于0、0.25、0.5、1、1.5、2、3、4、6、8、12 h采血,HPLC-MS/MS法测定荷叶碱血药浓度,计算主要药动学参数。结果最佳处方为荷叶碱用量20 mg,磷脂酰胆碱与胆固醇比例5∶1,脂药比12∶1,DSPE-mPEG2000用量30 mg,水化温度40℃,超声时间15 min,平均包封率为71.69%,载药量为4.59%,粒径为161.84 nm,PDI为0.163,Zeta电位为-7.17 mV。DSPE-mPEG2000修饰后,荷叶碱在人工胃液、人工肠液中48 h内累积释放度分别为66.17%、53.90%。与原料药比较,脂质体t_(max)、t_(1/2)延长(P<0.01),C_(max)、AUC_(0~t)、AUC_(0~∞)升高(P<0.01),相对生物利用度增加至6.14倍。结论DSPE-mPEG2000修饰脂质体可促进荷叶碱口服吸收。
AIM To prepare distearoyl phosphoethanolamine-polyethylene glycol 2000(DSPE-mPEG2000)-modified nuciferine liposomes,and to investigate their in vivo pharmacokinetics.METHODS Film-ultrasonic method was used to prepare liposomes.With phosphatidylcholine-cholesterol ratio,lipid-drug ratio,DSPE-mPEG2000 consumption,hydration temperature and ultrasonic time as influencing factors,the formulation was optimized by single factor test,after which the encapsulation efficiency,drug loading,particle size,PDI,Zeta potential and in vitro drug release were determined.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of nuciferine and nuciferine liposomes with or without DSPE-mPEG2000 modification(20 mg/kg),respectively,after which the blood collection was made at 0,0.25,0.5,1,1.5,2,3,4,6,8,12 h,HPLC-MS/MS was adopted in the plasma concentration determination of nuciferine,and main pharmacokinetic parameters were calculated.RESULTS The optimum formulation was determined to be 20 mg for nuciferine consumption,5∶1 for phosphatidylcholine-cholesterol ratio,12∶1 for lipid-drug ratio,30 mg for DSPE-mPEG2000 consumption,40℃for hydration temperature,and 15 min for ultrasonic time,the average encapsulation efficiency,drug loading,particle size,PDI and Zeta potential were 71.69%,4.59%,161.84 nm,0.163 and-7.17 mV,respectively.After being modified by DSPE-mPEG2000,the accumulative release rates within 48 h of nuciferine in artificial gastric juice and artificial intestinal juice were 66.17%and 53.90%,respectively.Compared with raw medicine,the liposomes displayed prolonged t_(max),t_(1/2)(P<0.01)and increased C_(max),AUC_(0-t),AUC_(0-∞)(P<0.01),and the relative bioavailability was enhanced to 6.14 times.CONCLUSION(DSPE-mPEG2000)-modified liposomes can promote the oral absorption of nuciferine.
作者
李燕红
张春燕
陈乾
LI Yan-hong;ZHANG Chun-yan;CHEN Qian(Huanghe Science and Technology College,Zhengzhou 450005,China;The Hospital Affiliated to Huanghe Science and Technology College,Zhengzhou 450000,China;The Second Hospital Affiliated to Henan University of Chinese Medicine,Zhengzhou 450002,China)
出处
《中成药》
CAS
CSCD
北大核心
2023年第8期2457-2464,共8页
Chinese Traditional Patent Medicine
基金
国家自然科学基金(82104833)。
