柚皮素固体脂质纳米粒制剂的制备、表征及药动学评价  

Formulation,characterization,and pharmacokinetics of solid lipid nanoparticles loaded with naringenin

作　　者：卞龙艳[1] 

机构地区：[1]盐城卫生职业技术学院,盐城224005

出　　处：《中国新药杂志》2016年第12期1424-1430,共7页Chinese Journal of New Drugs

摘　　要：目的:制备柚皮素固体脂质纳米粒冻干粉,考察其理化性质及经大鼠肺部给药后的体内药动学行为。方法:采用乳化蒸发-低温固化法,以包封率为考察指标,正交试验优化其处方并考察其粒径、形态、电位及体外释放。以外观,色泽,再分散性为考察指标筛选最佳冻干保护剂,采用傅里叶红外光谱(FT-IR)分析药物在纳米粒中的理化性质。通过肺部给药考察柚皮素固体脂质纳米粒和柚皮素溶液在大鼠体内的药动学行为。结果:柚皮素固体脂质纳米粒外观呈球形,分布比较均匀,平均粒径为(134.81±14)nm,多分散系数(PDI)为0.238,Zeta电位为(-27.6±0.87)m V,包封率为(81.2±1.6)%,载药量为(8.11±0.5)%(n=3),5%甘露醇为冻干保护剂最好,药物和载体间属于物理吸附,体外溶出实验表明柚皮素固体脂质纳米粒与原料药相比具有明显的缓释作用。柚皮素原料药和纳米粒的Cmax分别为(173.00±25.05)和(280.00±36.34)ng·m L^(-1),t1/2分别为(5.23±0.22)和(19.03±8.00)h,AUC0~t分别为(939.32±190.18)和(3 440.23±533.88)ng·m L^(-1)·h,MRT分别为(7.29±0.44)和(24.29±9.27)h。结论:本文成功研制了柚皮素固体脂质纳米粒新剂型,体外释药结果表明该制剂具有明显的缓释作用,改善了其溶解度和稳定性差的缺陷,提高了药物的体内生物利用度,为肺部给药系统提供了适宜的新剂型,因此,柚皮素固体脂质纳米粒是一种具有研究潜质的适合肺部给药系统的新剂型。Objective： To prepare naringenin-loaded solid lipid nanoparticles（ NRG-SLNs） lyophilized powder,and investigate its physicochemical properties,release characteristics,and the pharmacokinetic characteristics in rats after pulmonary delivery. Methods： NRG-SLNs were prepared by solvent emulsification-evaporation method,the the formulation was optimized by orthogonal design with encapsulation efficiency as indicator. The particle size,morphology,Zeta potential,polydispersity index（ PDI）,and in vitro drug release behavior were determined. The appearance and color of lyophilized powder were evaluated with FT-IR analysis. The pulmonary pharmacokinetics of NRG-SLNs in rats was studied after pulmonary instillation. Results： The NRG-SLNs showed spherical shape with an even distribution of diameter. The particle size was（ 134. 81 ± 14） nm,PDI was 0. 238,Zeta potential was（-27.6 ±0.87） m V,entrapment efficiency was（81.2 ± 1. 6） %,and drug loading was（8.11±0.5） %（n=3）.5% mannitol was the best protective agent for the preparation of NRG-SLNs lyophilized powder. It was indicated that the drug was dispersed in amorphous state in SLNs. The dissolution experiments showed that NRG-SLN hadobviously sustained release compared with the bulk drug. After pulmonary administration to rats,the pharmacokinetic parameters of naringenin liposomes and solution were as follows： Cmax（ 173. 00 ± 25. 05） and（ 280. 00 ± 36. 34）ng·mL^-1,AUC0-t（ 939.32 ± 190.18） and（ 3 440.23 ± 533.88） ng·m L^-1·h,MRT（ 7.29 ± 0.44） and（ 24.29 ±9.27） h,respectively. Conclusion： Naringenin solid lipid nanoparticles were successfully developed in this study.The in vitro drug release experiments showed that the preparation has obvious sustained-release effect,which overcame the bad solubility and stability of naringenin and improved the in vivo bioavailability,thus providing a suitable new dosage forms for pulmonary drug delivery. Therefore,naringenin solid lipid nanoparticles is a new dosage form

关 键 词：柚皮素 固体脂质纳米粒 体外释放 冷冻干燥 药动学 

分 类 号：R943.41[医药卫生—药剂学]