【摘要】 目的采用乳化溶剂挥发法制备白藜芦醇聚乳酸羟基乙酸[poly(lactic-co-glycolic acid),PL-GA]长效微球,评价各因素对微球性质的影响。方法以微球的包封率、载药量、突释和粒径作为微球的质量评价指标,研究分散相与连续相的体积比、PLGA浓度、聚乙烯醇(polyvinyl alcohol,PVA)浓度、搅拌速度对微球性质的影响,并优化白藜芦醇PLGA微球的制备工艺。结果分散相与连续相的体积比为1∶50时,包封率高,但4 h突释量达到76%,当分散相与连续相体积比由1∶50提升到1∶150时,突释降低了22%;随着聚合物浓度的增加粒径明显增大,突释显著降低;理论载药量对粒径影响不大,在高载药量时突释显著减少;搅拌速度的增加使粒径减小,突释增加;PVA浓度的增加对粒径没有明显的影响,但当PVA的质量浓度从1 g.L-1增加到5 g.L-1时,包封率从93.57%降低到80.31%。结论分散相与连续相的体积比、PLGA浓度、PVA浓度、搅拌速度对微球性质有很大的影响。优化条件下制备的微球形态完整,载药量为(27.86±1.00)%,包封率为(93.57±2.87)%,平均粒径约为21.12μm。白藜芦醇PLGA微球体外释放25 d的累积释药率达(94.04±4.94)%,有望研制成1个月给药1次的给药系统。更多还原

【Abstract】 Objective To prepare trans-resveratrol(t-Rev)loaded poly(lactic-co-glycolic acid)(PLGA) microspheres by the oil-in-water(o/w)emulsification solvent evaporation method,and evaluate factors influencing properties of the microspheres.Methods Using entrapment efficiency,drug loading,burst release and particle size as the criteria,effects of diapersed phase/continuous phase(DP/CP)ratio,PLGA concentration,theoretical drug loading,PVA concentration and homogenization speed on the characteristics of the microspheres were investigated and preparation process was optimized.Results DP/CP was a critical factor in preparing microspheres.When DP/CP ratio was 1∶50,encapsulation efficiency was high,but with a high burst release of 76%.When DP/CP ratio increased from 1∶50 to 1∶150,the burst release decreased by 22%.Increase in PLGA concentration led to increased particle sizes and decreased burst release.Theoretical drug loading had no significant influence on particle size,with decreased burst release at higher drug loading of 40%.Increase in homogenization speed led to decreased particle size with increased burst release.PVA concentration had no influence on particle size but the encapsulation efficiency decreased from 93.57% to 80.31% when increasing PVA concentration from 1 g·L-1to 5 g·L-1.Conclusions The DP/CP ratio,PLGA concentration,theoretical drug loading,PVA concentration and homogenization speed have a significant influence on the properties of resveratrol loaded PLGA microspheres.The microspheres are smooth and spherical with the drug loading of(27.86±1.00)%,the entrapment efficiency of(93.57±2.87)% and the mean diameter of 21.12 μm.t-Rev can be slowly released from PLGA microspheres for over 25 days.更多还原