桔皮素固体脂质纳米粒制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics of tangeretin solid lipid nanoparticles

作　　者：杨丽萍 李伟宏 YANG Li-ping;LI Wei-hong(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》2023年第11期3520-3527,共8页Chinese Traditional Patent Medicine

基　　金：河南省高等学校重点科研计划项目(23B320013);河南应用技术职业学院“青年骨干教师”项目(2022-GGJS-H002);河南应用技术职业学院“首席技师”项目(2022-SXJS-HL01)。

摘　　要：目的制备桔皮素固体脂质纳米粒,并考察其体内药动学。方法熔融-高压均质法制备固体脂质纳米粒。以脂(单硬脂酸甘油酯)药比、泊洛沙姆188用量、Labrasol用量、均质压力、均质次数为影响因素,包封率、载药量为评价指标,单因素试验优化处方。在透射电镜下观察形态,测定溶解度、体外释药、稳定性,进行晶型分析。30只大鼠随机分为5组,分别灌胃给予桔皮素、物理混合物、桔皮素固体脂质纳米粒(不含Labrasol)、Labrasol+桔皮素固体脂质纳米粒、桔皮素固体脂质纳米粒(含Labrasol)的0.5%CMC-Na混悬液(50 mg/kg),于0.5、1、2、3、4、5、6、8、12 h采血,HPLC法测定桔皮素血药浓度,计算主要药动学参数。结果最佳处方为桔皮素用量30 mg,脂药比15∶1,泊洛沙姆188用量1.0%,Labrasol用量0.16%,均质压力80 MPa,均质次数6次,平均包封率为(90.16±1.67)%,载药量为(5.66±0.24)%,粒径为(189.76±8.92)nm,Zeta电位为-(36.08±1.72)mV。固体脂质纳米粒增加了桔皮素在模拟胃液、模拟肠液中的溶解度,120 min、12 h内累积释放度分别为39.79%、74.56%。桔皮素以无定形状态存在于固体脂质纳米粒中,冻干粉在6个月内稳定性良好。与原料药比较,固体脂质纳米粒(不含Labrasol)、Labrasol+固体脂质纳米粒、固体脂质纳米粒(含Labrasol)t_(max)、t_(1/2)延长(P<0.05),C_(max)、AUC_(0~t)、AUC_(0~∞)升高(P<0.05,P<0.01),其中AUC_(0~t)、AUC_(0~∞)以固体脂质纳米粒(含Labrasol)更明显(P<0.05),相对生物利用度分别增加至3.13、3.41、4.10倍。结论固体脂质纳米粒可改善桔皮素口服生物利用度,引入Labrasol后更明显。AIM To prepare tangeretin solid lipid nanoparticles,and to investigate their in vivo pharmacokinetics.METHODS Melting-high pressure homogenization method was adopted in the preparation of solid lipid nanoparticles.With lipid(glyceryl monostearate)-drug ratio,poloxamer 188 consumption,Labrasol consumption,homogeneous pressure and homogeneous frequency as influencing factors,encapsulation efficiency and drug loading as evaluation indices,the formulation was optimized by single factor test.The morphology was observed under transmission electron microscope,after which the solubility,in vitro drug release and stability were determined,crystal form analysis was performed.Thirty rats were randomly assigned into five groups and given intragastric administration of the 0.5%CMC-Na suspensions of tangeretin,physical mixture,tangeretin solid lipid nanoparticles(free of Labrasol),Labrasol+tangeretin solid lipid nanoparticles and tangeretin solid lipid nanoparticles(containing Labrasol)(50 mg/kg),respectively,after which blood collection was made at 0.5,1,2,3,4,5,6,8,12 h,HPLC was adopted in the plasma concentration determination of tangeretin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 30 mg for tangeretin consumption,15∶1 for lipid-drug ratio,1.0%for poloxamer 188 consumption,0.16%for Labrasol consumption,80 MPa for homogeneous pressure,and 6 times for homogeneous frequency,the average encapsulation efficiency,drug loading,particle size and Zeta potential were(90.16±1.67)%,(5.66±0.24)%,(189.76±8.92)nm and-(36.08±1.72)mV,respectively.Solid lipid nanoparticles increased the solubilities of tangeretin in simulated gastric juice and simulated intestinal juice,whose accumulative release rates were 39.79%and 74.56%within 120 min and 12 h,respectively.Tangeretin existed in solid lipid nanoparticles in an amorphous state,whose lyophilized powder demonstrated good stability within six months.Compared with raw medicine,the solid lipid nanoparticles(free of Labrasol),La

关 键 词：桔皮素 固体脂质纳米粒 制备 体内药动学 熔融-高压均质法 HPLC 

分 类 号：R944[医药卫生—药剂学]