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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 the naringenin solid lipid nanoparticles freeze-dried powder and investigate its physicochemical properties and in vivo pharmacokinetics after pulmonary administration in rats. Methods: Emulsion evaporation - low temperature curing method was used to investigate the entrapment efficiency. Orthogonal test was used to optimize its formulation and study its particle size, morphology, potential and in vitro release. The appearance, color and redispersibility were selected as the best lyoprotectants, and the physicochemical properties of the drug in the nanoparticles were analyzed by Fourier transform infrared spectroscopy (FT-IR). Pharmacokinetics of naringenin solid lipid nanoparticles and naringenin solution in rats was investigated by pulmonary administration. Results: The appearance of naringin solid lipid nanoparticles was spherical with an average particle size of (134.81 ± 14) nm, a polydispersity index (PDI) of 0.238 and a Zeta potential of (-27.6 ± 0.87) m V, The entrapment efficiency was (81.2 ± 1.6)%, drug loading was (8.11 ± 0.5)% (n = 3), and 5% mannitol was the best lyoprotectant. The drug and the carrier were physical adsorption and in vitro dissolution experiment Naringenin solid lipid nanoparticles showed that compared with the drug substance has a significant sustained-release effect. The Cmax of the naringenin and the nanoparticles were (173.00 ± 25.05) and (280.00 ± 36.34) ng · m L -1, respectively, and the values of t 1/2 were (5.23 ± 0.22) and (19.03 ± 8.00) h (939.32 ± 190.18) and (3440.23 ± 533.88) ng · m L -1 · h, respectively. The MRT was (7.29 ± 0.44) and (24.29 ± 9.27) h respectively. CONCLUSIONS: A new dosage form of naringenin solid lipid nanoparticles was successfully developed in this paper. The in vitro drug release results showed that the preparation has obvious sustained release effect, improved its solubility and stability defects, improved the in vivo bioavailability of the drug, Therefore, the naringenin solid lipid nanoparticles are a new dosage form suitable for the pulmonary administration system with research potential.