目的 研究壳聚糖包衣姜黄素醇质体(chitosan coated curcumin ethosomes,CMETS-CS)的体外释药特性和大鼠体内药动学特性。方法 采用动态透析法考察CMETS-CS在2种介质(pH 1.2 HCl和pH 6.8 PBS溶液)中的体外累积释放率,通过相似因子法评价释药行为;大鼠灌胃给药后,采用高效液相色谱法(high performance liquid chromatography,HPLC)测定各时间点血药浓度,绘制药-时曲线,通过DAS软件处理并计算药动学参数及生物等效性。结果 CMETS-CS在pH 1.2 HCl和pH 6.8 PBS溶液中的累积释放率分别为(70.49±0.75)%和(73.90±0.52)%,与CM相比明显增加体外释药量。此外,CMETS-CS在2种释放介质中的释放行为具有相似性。经计算后,CMETS-CS的0~72 h曲线下面积(AUC0-72 h)、平均滞留时间(MRT0-72 h)、峰浓度(ρmax)分别为游离姜黄素(curcumin,CM)的11.84、5.45和1.55倍,其CMETS-CS的相对生物利用度为1 111.32%。CMETS-CS和CM的AUC0-72 h、AUC0-∞和tmax生物不等效,但ρmax生物等效。结论 与CM相比,CMETS-CS可改善体外释药行为,显著提高口服生物利用度,且生物不等效。
Abstract
OBJECTIVE To investigate the release characteristics in vitro of chitosan coated curcumin ethosomes (CMETS-CS) and its pharmacokinetics in rats. METHODS The in vitro cumulative release rate of CMETS-CS in two different media (pH 1.2 HCl and pH 6.8 PBS solution) was investigated by dynamic dialysis. The release behavior was evaluated by similar factor method. After gastrointestinal administration, the plasma drug concentration at different time point was determined by high performance liquid chromatography (HPLC), and the average plasma concentration-time curve was drawn. The pharmacokinetic parameters, bioequivalence between CMETS-CS and CM were analyzed by DAS software. RESULTS The cumulative release rates of CMETS-CS in pH 1.2 HCl and pH 6.8 PBS solution were (70.49±0.75)%, (73.90±0.52)%, respectively. Compared with CM, the CMETS-CS significantly increase the drug release.The release behavior of CMETS-CS in the two different release media was similar. After calculation, the area under the 0-72 h curve (AUC0-72 h), mean residence time (MRT0-72 h), peak concentration (ρmax) of CMETS-CS were 11.84, 5.45, 1.55 times than those of free curcumin (CM), respectively and its relative bioavailability of CMETS-CS was 1 111.32%. The bioequivalence of AUC0-72 h、AUC0-∞ and tmax and in CMETS-CS and CM were not eligible, but bioequivalence of ρmax was eligible. CONCLUSION Compared with free curcumin, CMETS-CS can improve the release behavior in vitro, significantly improve the oral bioavailability in rats, and there is not bioequivalence between CMETS-CS and CM.
关键词
姜黄素 /
醇质体 /
壳聚糖 /
体外释药 /
药动学 /
生物等效性
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Key words
curcumin /
ethosome /
chitosan /
in vitro release /
pharmacokinetics /
bioequivalence
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中图分类号：
R944
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基金
重庆市社会事业与民生保障科技创新专项资助(cstc2017shmsA130028);重庆市研究生科研创新项目资助(CYS19210)
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