氟尿苷二丁酸酯固体脂质纳米粒的制备和肝靶向性研究

采用薄膜-超声分散法制备氟尿苷二丁酸酯(FUDRB)固体脂质纳米粒(FUDRB-SLN)和半乳糖苷(G₂)修饰的FUDRB-SLN(FUDRB-G₂SLN)。透射电镜研究其形态及粒径分布；凝胶色谱法测定载药量、包封率。结果表明，FUDRB-SLN和FUDRB-G₂SLN的粒径分别为(137.5±11.1)nm和(95.0±10.7)nm，载药量分别为9.64%和8.56%，包封率分别为99.81%和96.23%。为比较其肝靶向作用，小鼠尾静脉给药后，HPLC法测定氟尿苷(FUDR)在血清及肝、 肾、 肺匀浆中的浓度，计算出FUDR-sol、 FUDRB-SLN和FUDRB-G₂SLN的肝靶向效率分别为2.56、 5.90和8.28。FUDRB-G₂SLN组480 min时在肝脏中仍可检测到FUDR。这些结果说明FUDRB-SLN和FUDRB-G₂SLN在小鼠体内具有良好的肝靶向性，G₂修饰的SLN是一种良好的药物载体，可使药物选择性地导向肝细胞，且具有缓释作用。

Preparation and liver targeting of floxuridinyl dibutyrate solid lipid nanoparticles

This paper described the preparation and liver targeting traits of new solid lipid nanoparticles (SLN) containing floxuridinyl dibutyrate (FUDRB) modified with beta-D-galactosides (G2). FUDRB-SLN and FUDRB-G2SLN were prepared by thin layer ultrasonic technique. Transmission electron microscopy micrograph analysis demonstrated that the particle sizes of FUDRB-SLN and FUDRB-G2SLN were (137.5 +/- 11.1) nm and (95.0 +/- 10.7) nm. Drug loading were 9.64% and 8.56%, and entrapment efficiency were 99.81% and 96.23%, respectively. The concentrations of floxuridine (FUDR) in serum and some organs (liver, kidney and lung) were determined by RP-HPLC after iv administration of SLN. FUDR release was confirmed, and a significant enrichment of SLN modified with G2 was observed in liver with G2 complex (targeting rates of SLN-G2 was 8.28 for liver) in comparison with FUDR-sol (targeting rate was 2.56). FUDR could be detected in liver in mice at 480 min after iv administration of FUDRB-G2SLN. These results suggested that incorporation of G2 (4%-5%, g/g) into SLN enhanced the liver targeting-ability of FUDRB. SLN containing G2 could be a useful drug carrier system for liver targeting.