载白藜芦醇PLGA纳米粒的制备及其体内外评价

Preparation and in Vitro/in Vivo Evaluation of Resveratrol Loaded PLGA Nanoparticles

目的通过聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米粒的负载,改善白藜芦醇(resveratrol,RES)体内清除快、作用时间短的缺陷,延长RES镇痛作用时间。方法利用复乳溶剂蒸发法制备PLGA纳米粒,载药后离心法除去游离药物;透射电镜考察其形态;激光粒度分析仪考察粒径、Zeta电位和稳定性;HPLC考察包封率和载药量;透析袋法考察其体外释药特性;热板法、醋酸扭体法及鼠尾测痛法考察其镇痛效果。结果制备的PLGA@RES分布均一,无团聚现象,粒径为(210.90±1.76)nm,多分散指数为0.22±0.02,Zeta电位为(–21.81±0.75)mV;包封率与载药量分别为(89.62±2.52)%与(9.15±0.73)%;PLGA@RES较RES体外突释降低,缓释特性明显;药效学试验结果表明PLGA@RES起效快的特性仍未改变,镇痛作用时间明显延长。结论 PLGA@RES解决了RES体内清除快、作用时间短的缺陷,经过缓释后的PLGA@RES可发挥持久的镇痛效果,是一种RES的潜在递药系统。

OBJECTIVE To prolong the analgesic effect time of resveratrol(RES) through the loading of poly(lactic-co-glycolic acid)(PLGA) nanoparticles to improve the ability of removing the defects of quick clearance and short action time. METHODS PLGA@RES nanoparticles was synthesized by double emulsion solvent evaporation method, and free drug was removed by centrifugation after loading;the shape was investigated by transmission electron microscope;laser particle size analyzer were used to determine the particle size, Zeta potential and stability;the entrapment efficiency and drug loading were measured by HPLC;the drug release behavior was studied by dialysis method;pharmacodynamics was studied by the acetic acid-writhing test, the hot-plate test and the tail pain test. RESULTS The prepared PLGA@RES had uniform distribution and no agglomeration, the mean particle size was(210.90±1.76)nm and polymer dispersity index was 0.22±0.02, Zeta potential was(–21.81±0.75)mV;the entrapment efficiency and drug loading were(89.62±2.52)% and(9.15±0.73)%;compared with RES, burst release in vitro of PLGA@RES decreased and sustained release was more obviously;the results of pharmacodynamics experiment showed that the characteristics of fast PLGA@RES effect remained unchanged, and the analgesic effect time was significantly prolonged. CONCLUSION The PLGA@RES is a prospective drug delivery system for solving the shortcomings of rapid clearance and short action time of RES. After sustained release, PLGA@RES can exert a lasting analgesic effect.