松果菊苷固体脂质纳米粒的制备及其在体肠吸收特性、体内药动学研究

Preparation, in situ intestinal absorption characteristics and in vivo pharmacokinetics of echinacoside-loaded solid lipid nanoparticles

目的制备松果菊苷固体脂质纳米粒,并考察其在体肠吸收特性、体内药动学。方法冷均质法制备固体脂质纳米粒,测定包封率、载药量、粒径、Zeta电位、油水分配系数、体外释药。建立大鼠在体单向肠灌流模型,测定十二指肠、空肠、回肠、结肠中K_(a)、P_(app)。12只大鼠随机分为2组,分别灌胃给予松果菊苷及其固体脂质纳米粒的0.5%CMC⁃Na混悬液(50 mg/kg),于0.25、0.5、1、1.5、2、3、4、6、8、12 h采血,HPLC法测定松果菊苷血药浓度,计算主要药动学参数。结果固体脂质纳米粒包封率为(80.24±1.53)%,载药量为(3.19±0.23)%,粒径为(237.77±9.14)nm,Zeta电位为(-18.71±2.24)mV,油水分配系数为0.807,36 h内累积释放度为84.06%。固体脂质纳米粒K_(a)、P_(app)在大鼠各肠段中均高于原料药(P<0.01)。与原料药比较,固体脂质纳米粒t_(max)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3.82倍。结论固体脂质纳米粒可促进松果菊苷肠道吸收,改善其口服吸收生物利用度。

AIM To prepare echinacoside⁃loaded solid lipid nanoparticles,and to investigate their in situ intestinal absorption characteristics and in vivo pharmacokinetics.METHODS Cold homogenization method was applied to preparing the solid lipid nanoparticles,after which the encapsulation efficiency,drug loading,particle size,Zeta potential,oil⁃water partition coefficient and in vitro drug release were determined.The rat single⁃pass intestinal perfusion model was established,then K_(a) and P_(app) in duodenum,jejunum,ileum and colon were determined.Twelve rats were given intragastric administration of the 0.5%CMC⁃Na suspensions of echinacoside and its solid lipid nanoparticles(50 mg/kg),respectively,after which blood collection was made at 0.25,0.5,1,1.5,2,3,4,6,8,12 h,HPLC was adopted in the plasma concentration determination of echinacoside,and main pharmacokinetic parameters were calculated.RESULTS The solid lipid nanoparticles demonstrated the encapsulation efficiency,drug loading,particle size,Zeta potential,oil⁃water partition coefficient and accumulative release rate within 36 h of(80.24±1.53)%,(3.19±0.23)%,(237.77±9.14)nm,(-18.71±2.24)mV,0.807 and 84.06%,respectively.The K_(a) and P_(app) of solid lipid nanoparticles were higher than those of raw medicine in various rat intestinal segments(P<0.01).Compared with raw medicine,the solid lipid nanoparticles displayed prolonged t_(max)(P<0.01)and increased C_(max),AUC_(0-t),AUC_(0-∞)(P<0.01),and the relative bioavailabiliy was enhanced to 3.82 times.CONCLUSION Solid lipid nanoparticles can promote the intestinal absorption of echinacoside and improve its bioavailability of oral absorption.