姜黄素维生素E聚乙二醇琥珀酸酯-聚乙二醇硬脂酸酯15胶束对姜黄素溶解度和口服生物利用度的影响

Effect of curcumin-micelles adopting vitamin E-TPGS and Solutol HS 15 as carriers on solubility and oral bioavailability of curcumin

目的以维生素E聚乙二醇琥珀酸酯(VE-TPGS)和聚乙二醇硬脂酸酯15(Solutol HS 15,SHS15)为载体制备姜黄素胶束,并研究该胶束对姜黄素溶解度和口服生物利用度的影响。方法采用薄膜分散法制备姜黄素胶束;通过胶束平均粒径、载药量、包封率等指标表征该胶束,同时测定姜黄素的溶解度;通过体外释放考察该胶束的释放特性;进一步通过大鼠实验评估胶束对姜黄素口服生物利用度的影响。结果当VE-TPGS与SHS15加入质量比为3∶7时,胶束粒径为(35.79±1.23)nm,多分散性指数(PDI)为0.12±0.03;在该条件下,胶束的载药量和包封率分别为9.34%和90.03%,姜黄素的溶解度达到2.03 mg/m L;体外释放实验中,胶束组较姜黄素组有缓慢释放特性;大鼠口服生物利用度实验中,胶束组较姜黄素组的相对生物利用度提高到303.5%(P<0.01)。结论本实验制备的胶束不仅有较好的缓释特性,还提高了姜黄素的溶解度和口服生物利用度。利用药物-胶束体系来改善难溶性药物的溶解度,具有较高的临床应用潜力。

Objective To prepare curcumin-micelles adopting vitamin E-TPGS（VE-TPGS） and Solutol HS15（SHS15） as carriers, and study the effect on solubility and oral bioavailability of curcumin（Cur）. Methods Cur was loaded into micelles between VE-TPGS and SHS15 by thin film dispersion method. Particle size, loading efficiency, entrapment efficiency, and in vitro release were carried on to estimate the influence of micelles on Cur; Moreover, oral bioavailability in rats was also evaluated. Results The particle size was（35.79 ± 1.23） nm with polydispersity index（PDI） of 0.12 ± 0.03 when the optimized micelles ratio was at 3：7 of VE-TPGS and SHS15, which increased the solubility of Cur to 2.03 mg/m L in water. The entrapment efficiency and drug loading were 90.03% and 9.34%, respectively. The in vitro release profile showed a sustained release property compared with that of Cur. In addition, the relative bioavailability of micelles（AUC0~∞） compared with that of Cur（AUC0~∞） was 303.5%（P 〈 0.01）. Conclusion The Cur-micelles combined use of VE-TPGS and SHS15 shows great potential clinical application.