PEG-PLGA载5-FU纳米缓释微球的制备及体外释药研究

Study on preparation and in vitro release of 5-fluorouracil loaded polylactide-co-glycolide-co-poly(ethylene glycol) nanoparticles

目的将5-FU(氟尿嘧啶)包裹于可生物降解性高分子聚合物PLGA(聚乳酸丙烯酸聚合物)中,构成具有缓释特性的纳米球,并于其表面以能阻止MPS细胞吞噬的亲水基团PEG(聚乙二醇)修饰,以达到适于体内长循环的载药体系。方法复乳法将氟尿嘧啶水相于二氯甲烷中均匀分散,形成W/O的初乳液,将该初乳液在高速搅拌下缓慢注入含5%(W/V)聚乙烯醇(PVA)的氟尿嘧啶饱和水溶液中,经乳化形成W/O/W乳液,旋转蒸发二氯甲烷溶剂使微球固化;冻干后在4℃冰箱中保存。结果纳米微球平均粒径310nm,表面光滑,直径分布均匀,5-FU载药量15.4%,缓释5d。结论制备得到了缓释时间为5d的5-FU载药纳米微球。

Objective To prepare a 5-fluorouracil carried system by PIGA nano-sphere,a material with biodegradability and ER（extended release） capability, of which surface was modified by hydrophilic group PEG to prolong NPs in vivo circulation. Methods High shearing emulsification was used to make the 5-fluorouracil intemal water phase dispersed uniformly in dichloromethane and the primary emulsion （W/O） was thus obtained.This was dripped into 5-FU saturated solution containing 5% （W/V） of PVA under a vigorous stirring for 5 min to obtain the double emulsion （W/O/W）. Mterwards, the solvent evaporation was carried out under vacuum, using a rotating evaporator to make the particle indurescent. Eventually lyophilized NPs was stored at 4℃. The morphology of the NPs was investigated by scanning electron microscopy（SEM） and loading efficiency was determined by thermo-gravimetric analysis （TGA）. Drew the curve of accumulative release rate on time by UV spectrophotometer. Results The average-diameter of 5-FU-PLGA-PEG-NP was 310nm, loading efficiency was 15.4%. In vitro release test showed that the release behavior of 5-FU from NPs in PBS was that after an obvious release of about 52.5% in former 24h, there were 99.2% 5-FU released within 5 days. Conclusion We adjust experiment factors such as polymer concentration, internal water phase volume, and emulsification time to prepare drug loaded NPs by W/O/W double emulsion. Investigation of drug loading efficiency and in vitro release shows that the 5-FU loaded NPs have well sphere morphology and 5-days control release properties.