包裹5-氟尿嘧啶的二氧化硅纳米颗粒的制备及细胞毒性研究

目的 制备包裹5-氟尿嘧啶的二氧化硅(5-Fu/SiO₂)纳米颗粒，并对其药剂学参数及体外细胞毒性进行研究。方法 利用反相微乳化法制备5-Fu/SiO₂纳米颗粒，对5-Fu投入量及反应时间等合成条件进行优化，考察纳米颗粒的稳定性及体外释药行为，并采用MTT法对其体外细胞毒性进行研究。结果 当5-Fu投入量为1.33 mg及反应时间为24 h时，5-Fu/SiO₂纳米的载药率及包封率达到最高，分别为1.03%及24.77%，同时该纳米在48 h内释放率达到41.31%，7 d内粒径无明显变化。细胞毒性实验表明，5-Fu/SiO₂纳米对人肝癌细胞具有明显的抑制效果，而空白SiO2纳米对细胞活性影响较小。结论 成功制备了稳定性好、缓释时间长的5-Fu/SiO₂纳米颗粒，为开发5-Fu缓释剂型提供了新的思路。

Synthesis of 5-Fluorouracil Doped Silica Nanoparticles and Their Cytotoxicity

OBJECTIVE To synthesize 5-fluorouracil(5-Fu) doped silica(5-Fu/SiO₂) nanoparticles, and to evaluate their parameter of pharmacy and cytotoxicity in vitro. METHODS The 5-Fu/SiO₂ nanoparticles were prepared in the water-in-oil microemulsion, and the administered dose of 5-Fu and the reaction time were optimized to improve the drug loading and entrapment efficiency. The stability and the in vivo release of 5-Fu/SiO₂ were also investigated. The antitumor activities in vitro were evaluated by MTT method. RESULTS With adding 1.33 mg 5-Fu and reacting 24 h, the 5-Fu loading and entrapment efficiency reached maximum yields as 1.03% and 24.77%, respectively. The 5-Fu was released slowly for 48 h, and the size of 5-Fu/SiO₂ nanoparticles had no obvious changing in 7 d. The MTT experiments showed that 5-Fu/SiO₂ nanoparticles had an inhibition on the human hepatic cancer cells, while the SiO₂ nanoparticles had no similar effects. CONCLUSION The 5-Fu/SiO₂ nanoparticles with a good stability and long release is prepared successfully, which provides a new fitting way for developing the 5-Fu dosage forms.