柚皮素-mPEG-PLA聚合物胶束的制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics of naringenin-loaded mPEG-PLA polymeric micelles

作　　者：王丽[1] 黄一聆[1] 房伟[2] WANG Li;HUANG Yi-ling;FANG Wei(Shangqiu Medical College,Shangqiu 476000,China;The First Hospital Affiliated to Henan University of Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]商丘医学高等专科学校,河南商丘476000 [2]河南中医药大学第一附属医院,河南郑州450000

出　　处：《中成药》2022年第4期1052-1057,共6页Chinese Traditional Patent Medicine

摘　　要：目的 制备柚皮素-[聚乙二醇单甲醚-聚乳酸(mPEG-PLA)]聚合物胶束,并考察其体内药动学。方法 采用溶剂挥发法制备聚合物胶束,测定其包封率、载药量、粒径、PDI、Zeta电位、体外释药。大鼠分别灌胃给予柚皮素及其聚合物胶束的0.5%CMC-Na溶液(20 mg/kg),于0、0.25、0.5、1、2、2.5、3、4、5、6、8、10、12 h采血,HPLC法测定柚皮素血药浓度,计算主要药动学参数。结果 最佳条件为柚皮素用量25 mg,mPEG-PLA用量150 mg,有机溶剂体积3 mL,水相体积20 mL,旋蒸温度30℃,旋蒸时间3.5 h,所得聚合物胶束平均包封率为86.76%,载药量为12.71%,粒径为68.27 nm,PDI为0.181,Zeta电位为-18.6 mV,48 h内累积溶出度为71.05%。与原料药比较,聚合物胶束t_(max)、t_(1/2)延长(P<0.01),C_(max)、AUC_(0~)_(t)、AUC_(0~∞)升高(P<0.01),相对生物利用度提高至4.38倍。结论 mPEG-PLA聚合物胶束可有效促进柚皮素口服吸收。AIM To prepare naringenin-loaded polyethylene glycol monomethyl ethers-polylactic acid(mPEG-PLA) polymeric micelles and to investigate their in vitro pharmacokinetics.METHODS Polymeric micelles were prepared by solvent volatilization method,after which their encapsulation efficiency,drug loading,particle size,PDI,Zeta potential and in vitro drug release were determined.Rats were given intragastric administration of the 0.5%CMC-Na solutions of naringenin and its polymeric micelles(12.5 mg/mL),respectively,after which blood collection was made at 0,0.25,0.5,1,2,2.5,3,4,5,6,8,10,12 h.HPLC was adopted in the plasma concentration determination of naringenin,and main pharmacokinetic parameters were calculated.RESULTS The optimal conditions were determined to be 25 mg for naringenin consumption,150 mg for mPEG-PLA consumption,3 mL for organic solvent volume,20 mL for aqueous phase volume,30 ℃ for rotary evaporation temperature,and 3.5 h for rotary evaporation time,the obtained polymeric micelles demonstrated the encapsulation efficiency,drug loading,particle size,PDI,Zeta potential and accumulative dissolution rate within 48 h of 86.76%,12.71%,68.27 nm,0.181,-18.6 mV and 71.05%,respectively.Compared with the raw medicine,the polymeric micelles exhibited prolonged t_(max),t_(1/2)(P<0.01) and increased C_(max),AUC_(0-)_(t),AUC_(0-∞)(P<0.01),whose relative bioavailability was enhanced to 4.38 times.CONCLUSION mPEG-PLA polymeric micelles can effectively promote the oral absorption of naringenin.

关 键 词：柚皮素 聚乙二醇单甲醚-聚乳酸(mPEG-PLA) 聚合物胶束 制备 体内药动学 溶剂挥发法 HPLC 

分 类 号：R944[医药卫生—药剂学]