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

关键词:  白藜芦醇  PLGA纳米粒  缓释  镇痛  体内外评价

Key words:  resveratrol  PLGA nanoparticles  sustained release  analgesia  in vivo and in vivo evaluation

摘要:

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。

Abstract:

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.