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目的:制备氟尿苷二醋酸酯固体脂质纳米粒(FUDRA-SLN)和半乳糖苷修饰的氟尿苷二醋酸酯固体脂质纳米粒(FUDRA-GSLN),比较二者的肝靶向作用。方法:合成半乳糖苷[Galβ1-(CH2CH2O)10-C18H37]和FUDRA-GSLN。采用薄膜超声分散法制备FUDRA-SLN和FUDRA-GSLN;透射电镜研究其形态及粒径分布;HPLC测定载药量、包封率。小鼠尾静脉给药后,HPLC测定氟尿苷(FUDR)在血清及肝、肾、肺中的浓度。结果:FUDRA-SLN和FUDRA-GSLN的粒径分布分别为(215.3±83.1)nm和(106.0±37.7)nm,载药量分别为8.20%和8.91%,包封率分别为98.27%和94.36%。FUDR-sol、FUDRA-SLN和FUDRA-GSLN的靶向效率分别为1.71,5.62和11.43。结论:FUDRA-SLN和FUDRA-GSLN在小鼠体内具有良好的肝靶向性,FUDRA-GSLN的作用强于FUDRA-SLN,对提高药物疗效,减少用量,降低不良反应有一定意义。
Objective: To prepare fluorouridine diacetate solid lipid nanoparticles (FUDRA-SLN) and galactoside modified fluorouridine diacetate solid lipid nanoparticles (FUDRA-GSLN), and to compare their liver targeting effects . Methods: Galactoside [Galβ1- (CH2CH2O) 10-C18H37] and FUDRA-GSLN were synthesized. FUDRA-SLN and FUDRA-GSLN were prepared by thin-film ultrasonic dispersion. Morphology and particle size distribution were observed by transmission electron microscopy. Drug loading and entrapment efficiency were determined by HPLC. After tail vein injection in mice, the concentration of fluorouridine (FUDR) in serum, liver, kidney and lungs was determined by HPLC. RESULTS: The particle size distributions of FUDRA-SLN and FUDRA-GSLN were (215.3 ± 83.1) nm and (106.0 ± 37.7) nm, respectively, and their drug loadings were 8.20% and 8.91%, respectively. The encapsulation efficiencies were 98.27% and 94.36% . The targeting efficiencies of FUDR-sol, FUDRA-SLN and FUDRA-GSLN were 1.71, 5.62 and 11.43, respectively. Conclusion: FUDRA-SLN and FUDRA-GSLN have good liver targeting in mice. The effect of FUDRA-GSLN is stronger than that of FUDRA-SLN. It is of great significance to improve the curative effect, reduce the dosage and reduce the adverse reactions.