辣椒素纳米结构脂质载体制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics of capsaicin nanostructured lipid carriers

作　　者：田莉 李伟宏 王风云 刘俊保[3] TIAN Li;LI Wei-hong;WANG Feng-yun;LIU Jun-bao(Zhengzhou Shuqing Medical College,Zhengzhou 450064,China;Zhengzhou University of Industrial Technology,Zhengzhou 450042,China;Henan Provincial People’s Hospital,Zhengzhou 450003,China)

机构地区：[1]郑州澍青医学高等专科学校,河南郑州450064 [2]河南应用技术职业学院,河南郑州450042 [3]河南省人民医院,河南郑州450003

出　　处：《中成药》2023年第5期1403-1409,共7页Chinese Traditional Patent Medicine

基　　金：2019年度河南省医学科技攻关计划联合共建项目(LHGJ20191524)。

摘　　要：目的制备辣椒素纳米结构脂质载体,并考察其体内药动学。方法高压均质法制备纳米结构脂质载体,测定其粒径、Zeta电位、体外释药。以脂药比、固液脂质比、乳化剂(聚乙二醇硬脂酸酯15)浓度为影响因素,包封率、载药量为评价指标,星点设计-效应面法优化处方工艺。18只大鼠随机分为3组,分别灌胃给予辣椒素、物理混合物、辣椒素纳米结构脂质载体的0.5%CMC-Na混悬液(15 mg/kg),于不同时间点采血,HPLC法测定辣椒素血药浓度,计算主要药动学参数。另取30只大鼠,随机分为空白组(生理盐水)、阳性对照组(50 mg/kg盐酸雷尼替丁)、辣椒素纳米结构脂质载体组(15 mg/kg),给药7 d后在倒置荧光显微镜下观察胃黏膜组织形态。结果最佳处方为脂药比18.5∶1,固液脂质比4∶1,乳化剂浓度1%,包封率为80.62%,载药量为3.96%,粒径为178.06 nm,Zeta电位为-36.14 mV,36 h内累积释放度为66.17%。与原料药、物理混合物比较,纳米结构脂质载体t max延长(P<0.05),C_(max)、AUC_(0~t)、AUC_(0-∞)升高(P<0.01),相对生物利用度增加至3.73倍。辣椒素纳米结构脂质载体组大鼠胃黏膜损伤程度明显小于阳性对照组。结论纳米结构脂质载体可安全有效地促进辣椒素体外释放、体内吸收。AIM To prepare capsaicin nanostructured lipid carriers and to investigate their in vivo pharmacokinetics.METHODS High-pressure homogenization method was adopted in the preparation of nanostructured lipid carriers,after which the particle size,Zeta potential and in vitro drug release were determined.With lipid-drug ratio,solid-liquid lipid ratio and emulsifier(polyoxyethylene stearate 15)concentration as influencing factors,encapsulation efficiency and drug loading as evaluation indices,the formulation process was optimized by central composite design-response surface method.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of capsaicin,physical mixture and capsaicin nanostructured lipid carriers(15 mg/kg),respectively,after which blood collection was made at different time points,HPLC was adopted in the plasma concentration determination of capsaicin,and main pharmacokinetic parameters were calculated.Another thirty rats were randomly assigned into blank group(normal saline),positive control group(50 mg/kg ranitidine hydrochloride)and capsaicin nanostructured lipid carriers group(15 mg/kg),then the histomorphology of gastric mucosa was observed under inverted fluorescence microscope after 7-day administration.RESULTS The optimal formulation was determined to be 18.5∶1 for lipid-drug ratio,4∶1 for solid-liquid lipid ratio,and 1%for emulsifier concentration,the encapsulation efficiency,drug loading,particle size,Zeta potential and accumulative release rate within 36 h were 80.62%,3.96%,178.06 nm,-36.14 mV and 66.17%,respectively.Compared with raw medicine and physical mixture,the nanostructured lipid carriers displayed prolonged t max(P<0.05)and increased C_(max),AUC_(0~t),AUC_(0-∞)(P<0.01),the relative bioavailability was enhanced to 3.73 times.The injury degree of rat gastric mucosa in the capsaicin nanostructured lipid carriers group was obvious smaller than that in the positive control group.CONCLUSION Nanostructured lipid carriers c

关 键 词：辣椒素 纳米结构脂质载体 制备 体内药动学 高压均质法 星点设计-效应面法 HPLC 

分 类 号：R944[医药卫生—药剂学]