柚皮素固体脂质纳米粒的制备及体内外初步评价

Preparation of naringenin solid lipid nanoparticles and its preliminary characteristics in vitro and in vivo

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）mV，（82．13±3．44）％和（8．31±O．21）％。体外释放表明NRG溶液在5h内基本释放完全，而NRG—SLN混悬液释放了约35％，24h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 naringenin （NRG）-loaded solid lipid nanoparticles （SLN） and to pre- liminarily evaluate its characteristics in vitro and in vivo. Methods： NRG-SLN was prepared by a solvent injection method. Their properties such as encapsulation efficiency, drug loading, particle size, and zeta potential and in vitro release were investigated. At the same time, we also used the human lung carcinoma cell line Calu-3 cells and SD rats to determine their cytotoxicity, cellular uptake and pharmacokinetics. Results： NRG-SLN was oval in shape, and uniform in particle size. The average diameter was （ 103.9 ±2.2） nm （ PDI = 0. 226 ± 0.02） ; zeta po- tential was （ -31.3 ± 3.1 ） mV, encapsulation efficiency and drug loading were （82.13 ± 3.44）% and （8.31 ± 0.21 ）% , respectively. The in vitro drug release was full for NRG solution within 5 h, while it was about 35% for NRG-SLN suspension and the cumulative release reached 80% in 24 h showing a significant sustained profile. DSC analysis showed that the drug exited in amorphous form. The experiments in Calu-3 cells showed that SLN carrier had no cytotoxicity, and it had better intracellular uptake in small particle size. After intragastric administration to rats, the oral bioavailability of NRG-SLN （ AUC0_ ~ ） was approximately 2.93-fold （ P 〈 0.05 ） higher than that of NRG solution. Conclusion： NRG-SLN is successfully prepared, which has no cytotoxicity, and improves water sol- ubility and bioavailability.