白屈菜红碱PLGA纳米粒的制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics of chelerythrine PLGA nanoparticles

作　　者：徐志杰 XU Zhi-jie(Weihai Ocean Vocational College,Shandong 264300,China)

机构地区：[1]威海海洋职业学院,山东威海264300

出　　处：《中成药》2022年第10期3091-3097,共7页Chinese Traditional Patent Medicine

基　　金：国家自然科学青年基金(51804021);山东省医药卫生科技发展计划项目(2017WS594)。

摘　　要：目的制备白屈菜红碱聚乳酸-羟基乙酸共聚物(PLGA)纳米粒,并考察其体内药动学。方法溶剂挥发法制备PLGA纳米粒,XRPD进行晶型分析,测定溶解度、体外释药。以表面活性剂种类和浓度、PLGA用量、超声功率、超声时间为影响因素,包封率、载药量、粒径为评价指标,单因素试验优化制备工艺。大鼠随机分为2组,分别灌胃给予白屈菜红碱及其PLGA纳米粒的0.5%CMC-Na混悬液,于不同时间点采血,HPLC法测定白屈菜红碱血药浓度,计算主要药动学参数。结果最佳条件为白屈菜红碱用量30 mg,PLGA用量400 mg,表面活性剂(F68)浓度1%,超声功率300 W,超声时间12 min,平均包封率为(83.71±1.73)%,载药量为(5.76±0.27)%,粒径为(231.82±15.73)nm,PDI为0.101±0.014,Zeta电位为(-17.11±1.94)mV。白屈菜红碱以无定形状态存在。PLGA纳米粒溶解度为原料药的13.4倍,72 h内累积释放度为81.07%。与原料药比较,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),生物利用度增加至4.08倍。结论PLGA纳米粒可促进白屈菜红碱体外溶出,提高其口服生物利用度。AIM To prepare chelerythrine poly(lactic-co-glycolic acid)(PLGA)nanoparticles and to investigate their in vivo pharmacokinetics.METHODS The PLGA nanoparticles prepared by solvent evaporation method,then the crystal form analysis was performed by XRPD,and their dissolution rate and in vitro drug release were determined.With surfactant type and concentration,PLGA consumption,ultrasonic power and ultrasonic time as influencing factors,encapsulation efficiency,drug loading and particle size as evaluation indices,single factor test was applied to optimizing the preparation process.Rats were randomly assigned into two groups and given intragastric administration of the suspensions of ginsenoside Re and itsβ-cyclodextrin inclusion complex(100 mg/kg),respectively,after which blood collection was made at different time points,HPLC was adopted in the plasma concentration determination of chelerythrine,and main pharmacokinetic parameters were calculated.RESULTS The optimal conditions were determined to be 30 mg for chelerythrine consumption,400 mg for PLGA consumption,1%for surfactant(F68)concentration,300 W for ultrasonic power,and 12 min for ultrasonic time,the average encapsulation efficiency,drug loading,particle size,PDI and Zeta potential were(83.71±1.73)%,(5.76±0.27)%,(231.82±15.73)nm,0.101±0.014 and(-17.11±1.94)mV,respectively.Chelerythrine existed in an amorphous state.The solubility of PLGA nanoparticles was 13.4 times as high as that of raw medicine,with the accumulative release rate within 72 h of 81.07%.Compared with raw medicine,the PLGA nanoparticles displayed prolonged t_(max)and t_(1/2)(P<0.01),and increased C_(max),AUC _(0-t) and AUC _(0-∞)(P<0.05),the relative bioavailabiliy was enhanced to 4.08 times.CONCLUSION PLGA nanoparticles can promote the in vitro dissolution of chelerythrine and elevate its oral bioavailability.

关 键 词：白屈菜红碱 聚乳酸-羟基乙酸共聚物(PLGA)纳米粒 制备 体内药动学 溶剂挥发法 HPLC 

分 类 号：R944[医药卫生—药剂学]