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目的:制备柚皮素固体脂质纳米粒(NRG-SLN),并对其体外和体内的性质进行初步评价。方法:采用溶剂注入法制备NRG-SLN,并对其包封率、载药量、粒径、Zeta电位和体外释放率等性质进行考察,同时采用人肺癌细胞系Calu-3细胞和SD大鼠分别进行细胞毒性、细胞摄取和药动学研究。结果:NRG-SLN为椭圆形大小均匀的粒子,平均粒径、Zeta电位、包封率和载药量分别为(103.9±2.2)nm(PDI=0.226±0.02),(-31.3±3.1)m V,(82.13±3.44)%和(8.31±0.21)%。体外释放表明NRG溶液在5 h内基本释放完全,而NRG-SLN混悬液释放了约35%,24 h累积释放达到80%,有明显的缓释效果。DSC分析表明药物以无定型形式存在。细胞实验说明固体脂质纳米粒载体没有细胞毒性,粒径小、摄取效果较好。体内试验表明NRG-SLN口服生物利用度(AUC0~∞)比NRG原料药高了约2.93倍(P<0.05)。结论:本实验成功制备了无细胞毒性的NRG-SLN,提高了NRG的水溶性和体内生物利用度。
Objective: To prepare naringin solid lipid nanoparticles (NRG-SLN) and to evaluate its in vitro and in vivo properties. Methods: NRG-SLN was prepared by solvent injection. The entrapment efficiency, drug loading capacity, particle size, Zeta potential and in vitro release rate were investigated. At the same time, the human lung cancer cell line Calu-3 cells and SD rats Cytotoxicity, cellular uptake and pharmacokinetic studies were performed. RESULTS: NRG-SLN was an oval-shaped particle with average particle size, zeta potential, entrapment efficiency and drug loading of (103.9 ± 2.2) nm (PDI = 0.226 ± 0.02) and (-31.3 ± 3.1) m V, (82.13 ± 3.44)% and (8.31 ± 0.21)% respectively. In vitro release showed that NRG solution was almost completely released within 5 h, while NRG-SLN suspension released about 35%, cumulative release reached 80% after 24 h, which showed a significant release effect. DSC analysis showed that the drug exists in amorphous form. Cell experiments show that solid lipid nanoparticles carrier is not cytotoxic, small particle size, better intake. In vivo tests showed that oral bioavailability (AUC0 ~ ∞) of NRG-SLN was about 2.93 times higher than that of NRG drug substance (P <0.05). Conclusion: The cytotoxicity of NRG-SLN was successfully prepared in this experiment, which improved the water solubility and in vivo bioavailability of NRG.