负载胡桃醌的白及多糖-维生素E琥珀酸酯聚合物胶束的制备及表征

Preparation and characterization of Bletilla striata polysaccharide-vitamin E succinate polymer micelles loaded with juglone

目的制备负载胡桃醌的白及多糖-维生素E琥珀酸酯聚合物胶束(Jug/BSP-VES),并进行表征和评价。方法通过酯化反应合成白及多糖-维生素E琥珀酸酯聚合物(BSP-VES)载体,采用溶剂挥发法制备胶束,以包封率、载药量为指标,采用单因素实验筛选胶束处方和工艺,并用星点设计-效应面法确定其最优处方;使用透射电子显微镜和Zetasizer Nano ZSE纳米粒度电位仪观察测定Jug/BSP-VES形态、粒径、多分散指数(polydispersity index,PDI)及ζ电位;通过体外释药对Jug/BSP-VES进行评价,并考察其稳定性。结果成功合成BSP-VES聚合物,其临界聚集浓度(critical aggregation concentration,CAC)值为5.95μg/mL;以最优处方制备的Jug/BSP-VES胶束呈类球形,外观澄清透明,丁达尔效应明显;粒径、PDI、ζ电位结果分别为(120.30±2.80)nm、0.169±0.014、(−27.00±1.25)mV,包封率(89.140±1.163)%,载药量(6.493±0.087)%,在含有0.5%聚山梨酯-80的醋酸-醋酸钠缓冲液(pH 4.5)中48 h累积释放率达到(82.13±2.51)%。在4℃下储存稳定性良好。结论通过溶剂挥发法制备的Jug/BSP-VES胶束粒径均一,包封率高,稳定性较好,具有一定缓释作用,该研究为胡桃醌的递药系统设计提供了参考。

Objective Bletilla striata polysaccharide-vitamin E succinate polymeric micelles(Jug/BSP-VES)loaded with juglone were prepared,characterized and evaluated.Methods Bletilla striata polysaccharide-vitamin E succinate polymer(BSP-VES)carriers were synthesized by esterification reaction,and micelles were prepared by solvent evaporation method.The micellar prescriptions and processes were screened by single factor experiment using envelopment efficiency and drug loading as the indexes and the optimal prescription was determined by central composite design-response surface method.The morphology,particle size,polydispersity index(PDI)andζpotential of Jug/BSP-VES were observed and determined by transmission electron microscope and Zetasizer Nano ZSE nanoparticle size potentiostat,and Jug/BSP-VES was evaluated by in vitro drug release and its stability was examined.Results The BSP-VES polymer was successfully synthesized,and its critical aggregation concentration(CAC)value was 5.95μg/mL.The Jug/BSP-VES micelles prepared with the optimal prescription were spherical in shape,with a clear and transparent appearance and obvious Tyndall effect.The results of particle size,PDI,andζpotential were(120.30±2.80)nm,0.169±0.014,and(−27.00±1.25)mV,respectively,with the envelopment efficiency of(89.140±1.163)%,and the drug loading of(6.493±0.087)%and the cumulative release rates of(82.13±2.51)%for 48 h in acetic acid-sodium acetate buffer(pH 4.5)containing 0.5%polysorbate-80.Its storage was stable at 4℃.Conclusion The Jug/BSP-VES micelles prepared by solvent evaporation method had uniform particle size,high envelopment efficiency,good stability,and some slow release effects.This study provides a reference for the design of the delivery system of juglone.