柚皮素-PLGA纳米粒的制备及其体内药动学研究

目的制备柚皮素-PLGA纳米粒,并考察其体内药动学。方法纳米沉淀法制备PLGA纳米粒,在单因素试验基础上采用正交试验优化处方,测定包封率、载药量、粒径、Zeta电位、体外释药。大鼠分别灌胃给予柚皮素及其PLGA纳米粒混悬液(40 mg/kg)后采血,HPLC法测定柚皮素血药浓度,计算主要药动学参数。结果最佳处方为PLGA型号75∶25,药物与载体比例1∶14,油相与水相比例1∶8,泊洛沙姆188质量分数0.75%。所得柚皮素-PLGA纳米粒包封率为(84.06±1.66)%,载药量为(5.21±0.53)%,平均粒径为(203.51±8.14)nm,Zeta电位为(-34.2±3.0)mV,36 h内累积释放度达81.07%,体外释药符合Weibull模型(r=0.987 2)。与原料药比较,PLGA纳米粒t_max延长(P<0.01),C_max、AUC_0~t、AUC_0~∞升高(P<0.01),相对生物利用度增加至4.12倍。结论 PLGA纳米粒可明显改善柚皮素口服生物利用度。

Preparation and in vivo pharmacokinetics of naringenin-PLGA nanoparticles

AIM To prepare naringenin-PLGA nanoparticles and to investigate their in vivo pharmacokinetics.METHODS The PLGA nanoparticles were prepared by nano-precipitation method,after which the formulation was optimized by orthogonal test on the basis of single factor test,and encapsulation efficiency,drug loading,particle size,Zeta potential and in vitro drug release were determined.Rats were given intragastric administration of the suspensions of naringenin and its PLGA nanoparticles(40 mg/kg),respectively,after which blood collection was made,HPLC was adopted in the plasma mass fraction determination of naringenin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 75∶25 for PLGA type,1∶14 for drug-carrier ratio,1∶8 for oil phase-water phase ratio,and 0.75% for Poloxamer 188 mass fraction.The obtained naringenin-PLGA nanoparticles demonstrated the encapsulation efficiency of(84.06±1.66)%,drug loading of(5.21±0.53)%,particle size of(203.51±8.14) nm,Zeta potential of(-34.2±3.0) mV,and accumlative release rate of 81.07% within 36 h,whose in vitro drug release accorded with Weibull model(r=0.987 2).Compared with the raw medicine,the PLGA nanoparticles displayed prolonged t_max(P<0.01) and increased C_max,AUC_0-t and AUC_0-∞(P<0.01),whose relative bioavailability was enhanced to 4.12 times.CONCLUSION PLGA nanoparticles can obviously improve the oral bioavailability of naringenin.