姜黄素缓释微球的制备及体外释放

Preparation and in vitro release of curcumin sustained-release microspheres

背景:姜黄素具有抑制炎症、促进轴突生长等作用,但存在半衰期短、清除速度快等问题。目的:制备姜黄素缓释微球,以达到缓慢持续释放姜黄素的效果。方法:以聚乳酸-羟基乙酸共聚物为原料,采用O/W乳化挥发法合成合成姜黄素缓释微球,预设载药率分别为10%和20%,设为1、2号微球;以左旋聚乳酸-聚己内酯共聚物聚合物为原料,采用O/W乳化挥发法合成合成姜黄素缓释微球,预设载药率分别为10%和20%,设为3、4号微球,扫描电镜观察微球的表面形态特征,高效液相色谱检测微球的载药量和包封率。将4组微球浸泡在含有1%十二烷基硫酸钠的PBS释放外液中,模拟生理环境检测姜黄素微球的缓释情况。结果与结论:①扫描电镜显示,3、4号姜黄素微球的粒径、形态均优于1、2号姜黄素微球。②3号微球的包封率高于其他3组微球(P<0.05,P<0.01),1、2、4号微球的包封率比较差异无显著性意义(P>0.05)。③2、3、4号微球的载药率高于1号微球(P<0.01),2、4号微球的载药率高于3号微球(P<0.01)。④3号姜黄素缓释微球的体外释放可持续14 d,其余3种微球的体外释放可持续21 d,1、3号微球的药物累积释放率高于2、4号微球,3号微球的姜黄素释放浓度高于1号微球。⑤结果表明,以左旋聚乳酸-聚己内酯共聚物为原料合成的预设载药率10%的姜黄素缓释微球,缓释效果最接近零级释放要求。

BACKGROUND:Curcumin can inhibit inflammation and promote axonal growth,but it has a short half-life and a fast clearance rate.OBJECTIVE:To prepare curcumin sustained-release microspheres to release curcumin slowly and continuously.METHODS:Curcumin sustained-release microspheres were synthesized by O/W emulsification volatilization method using polylactic acid-glycolic acid copolymer as raw material.The preset drug loading rates were 10%and 20%,respectively,and set as No.1 and No.2 microspheres.The curcumin sustained release microspheres were synthesized by O/W emulsification volatilization method using L-lactic acid-polycaprolactone copolymer as raw material.The preset drug loading rates were 10%and 20%,respectively,and the microspheres were set as No.3 and No.4.The surface morphology of the microspheres was observed by scanning electron microscopy,and the drug loading and encapsulation efficiency of the microspheres were determined by high performance liquid chromatography.Four groups of microspheres were immersed in PBS release solution containing 1%sodium dodecyl sulfate,and the sustained release of curcumin microspheres was detected under simulated physiological environment.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the particle size and morphology of No.3 and No.4 curcumin microspheres were better than those of No.1 and No.2 curcumin microspheres.(2)The encapsulation rate of No.3 microspheres was higher than that of the other three groups(P<0.05,P<0.01),and there was no significant difference in the encapsulation rate of No.1,2 and 4 microspheres(P>0.05).(3)The drug loading rates of No.2,3 and 4 microspheres were higher than that of No.1 microsphere(P<0.01),and the drug loading rates of No.2 and 4 microspheres were higher than that of No.3 microsphere(P<0.01).(4)The in vitro release of No.3 curcumin sustained-release microspheres lasted for 14 days,and the release of the other three kinds of microspheres lasted for 21 days.The cumulative release rate of No.1 and No.3 was higher than that of No.2 and No.4,and the curcumin release concentration of No.3 was higher than that of No.1.(5)The results showed that slow-release effect of the curcumin sustained-release microspheres with a preset loading rate of 10%prepared by L-lactic acid-polycaprolactone copolymer best meets the Zero order release requirements.