白藜芦醇mPEG-PLGA纳米粒的制备及其体内药动学、抗肿瘤活性研究  

Preparation, in vivo pharmacokinetics and anti-tumor activity of resveratrol mPEG-PLGA nanoparticles

作　　者：李伟宏 王风云 LI Wei-hong;WANG Feng-yun(Henan Vocational College of Applied Technology,Zhengzhou 450042,China)

机构地区：[1]河南应用技术职业学院,河南郑州450042

出　　处：《中成药》2022年第11期3409-3415,共7页Chinese Traditional Patent Medicine

基　　金：河南省高等学校重点科研计划项目(18A320081);2019年度河南省医学科技攻关计划联合共建项目(LHGJ20191524)。

摘　　要：目的制备白藜芦醇聚乙二醇单甲醚-聚乳酸-乙醇酸共聚物(mPEG-PLGA)纳米粒,并考察其体内药动学、抗肿瘤活性。方法乳化-溶剂挥发法制备mPEG-PLGA纳米粒,测定包封率、载药量、粒径、PDI、Zeta电位、体外释药。大鼠随机分为2组,分别灌胃给予白藜芦醇及其mPEG-PLGA纳米粒的0.5%CMC-Na混悬液(40 mg/kg),于0、0.25、0.5、1、2、2.5、3、4、6、8、12、24、36 h采血,HPLC法测定白藜芦醇血药浓度,计算主要药动学参数。荷人卵巢癌细胞株HO-8910PM裸鼠随机分为空白组(生理盐水)、阳性组(2 mg/kg顺铂)、白藜芦醇组(40 mg/kg)及白藜芦醇mPEG-PLGA纳米粒低、高剂量组(30、40 mg/kg),测量瘤体积、瘤重,计算抑瘤率。结果mPEG-PLGA纳米粒包封率为84.42%,载药量为3.84%,粒径为143.72 nm,PDI为0.121,Zeta电位为-6.7 mV,36 h内累积释放度为74.12%。与原料药比较,mPEG-PLGA纳米粒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3.56倍。与空白组比较,白藜芦醇mPEG-PLGA纳米粒各剂量组瘤重降低(P<0.01),并且高剂量组瘤体积、瘤重小于白藜芦醇组(P<0.01),抑瘤率更高。结论mPEG-PLGA纳米粒可增加白藜芦醇口服生物利用度及体内抑瘤作用。AIM To prepare resveratrol methoxy poly(ethylene glyeol)-poly(lactic-co-glycolic acid)(mPEG-PLGA)nanoparticles and to investigate their in vivo pharmacokinetics,anti-tumor activity.METHODS The mPEG-PLGA nanoparticles were prepared by emulsion-solvent evaporation method,after which the entrapment efficiency,drug loading,particle size,PDI,Zeta potential and in vitro drug release were determined.Rats were randomly assigned into two groups and given intragastric administration of the 0.5%CMC-Na suspensions of resveratrol and its mPEG-PLGA nanoparticles(40 mg/kg),respectively,after which blood collection was made at 0,0.25,0.5,1,2,2.5,3,4,6,8,12,24,36 h,HPLC was adopted in the plasma concentration determination of resveratrol,and main pharmacokinetic parameters were calculated.Nude mice bearing with human ovarian cancer cell line HO-8910PM were randomly assigned into blank group(normal saline),positive group(2 mg/kg cisplatin),resveratrol group(40 mg/kg)and resveratrol mPEG-PLGA nanoparticles low-dose,high-dose groups(30,40 mg/kg),whose tumor volume and tumor weight were measured,and tumor inhibition rate was calculated.RESULTS The mPEG-PLGA nanoparticles demonstrated the entrapment efficiency,drug loading,particle size,PDI,Zeta potential and accumulative dissolution rate within 36 h of 84.42%,3.84%,143.72 nm,0.121,-6.7 mV and 74.12%,respectively.Compared with raw medicine,the mPEG-PLGA nanoparticles 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 increased to 3.56 times.Compared with the blank group,the various doses of resveratrol mPEG-PLGA nanoparticles groups exhibited decreased tumor weight(P<0.01),and the tumor volume and tumor weight in the high-dose group were smaller than those in the resveratrol group(P<0.01)with higher tumor inhibition rate.CONCLUSION mPEG-PLGA nanoparticles can enhance the oral bioavailability and in vivo tumor-inhibition effect of resveratrol.

关 键 词：白藜芦醇 聚乙二醇单甲醚-聚乳酸-乙醇酸共聚物(mPEG-PLGA)纳米粒 制备 体内药动学 抗肿瘤活性 乳化-溶剂挥发法 HPLC HO-8910PM 

分 类 号：R944[医药卫生—药剂学]