姜黄素纳米脂质载体的制备及大鼠体内药代动力学

采用熔融-乳化法制备姜黄素(Cur)纳米脂质载体(Cur-NLC),并考察其形态、粒径、Zeta电位、包封率和载药量等理化性质,同时以透析法研究制剂的体外释药特性。测定Cur-NLC和Cur原料的混悬液经大鼠灌胃后的体内药代动力学行为,并通过DAS2.0软件计算药代动力学参数。结果显示,透射电镜观察Cur-NLC呈较规则类球体,平均粒径为(187.5±4.67)nm,Zeta电位为(-23.65±2.86)mV,包封率、载药量分别为(98.33±0.40)%和(4.59±0.19)%;Cur-NLC和Cur混悬液体外释药行为分别符合一级方程和Peppas方程,Cur-NLC在HCl(pH 1)和PBS(pH 6.8)中的36 h累积释放量分别为24.3%和19.2%,Cur混悬液的36 h累积释放量分别为90.2%和84.2%,说明Cur担载于纳米脂质体后具有明显的缓释特性。经大鼠灌胃后,Cur-NLC和Cur混悬液的AUC0-∞分别为(621.14±179.92)ng.h/mL和(32.49±3.55)ng.h/mL,cmax分别为(92.81±38.52)ng/mL和(5.39±0.13)ng/mL,Cur-NLC的AUC0-∞和cmax分别提高了19.12倍和17.22倍。因此,Cur-NLC对Cur起到很好的保护作用,避免了药物的渗漏,载药量和包封率均较高,能显著增强Cur在胃肠道的吸收,提高Cur的口服生物利用度。

Preparation and pharmacokinetics of curcumin nanostructured lipid carriers in rats

Curcumin (Cur) loaded nanostructured lipid carriers(Cur-NLC) was prepared by melt-emulsification method.The physicochemical properties such as morphology,particles size,Zeta potential,entrapment efficiency and drug-loading capability were evaluated.Dialysis method was employed to investigate the release of Cur-NLC in vitro.In addition,the pharmacokinetics in rats receiving oral dosing of Cur-NLC and Cur-dispersion was investigated by HPLC method and analyzed by DAS2.0 pharmacokinetic software.The result showed that Cur-NLC was quasi-spherical shapes observed by TEM and the mean particle size,Zeta potential,entrapment efficiency drug-loading capability and were (187.5±4.67)nm,(-23.65±2.86)mV,(98.33±0.40)% and (4.59±0.19)%,respectively.The cumulative release of Cur-NLC in 36 h was lower than that of Cur-dispersion in HCl (pH 1) and PBS (pH 6.8) (19.2% vs 84.2% and 24.3% vs 90.2%) and the release characteristic of Cur-NLC and Cur-dispersion displayed a first-order process and Peppas process,respectively.After oral administration the AUC and c_max of Cur-NLC were 19.12-fold and 17.22-fold higher than those of Cur-dispersion (621.14±179.92)ng·h/mL vs (32.49±3.55)ng·h/mL and (92.81±38.52)ng/mL vs (5.39±0.13) ng/mL.In conclusion,Cur-NLC exhibited high encapsulation efficiency and drug loading capability,possessed sustained release in vitro and improved the oral absorption and bioavailability of Cur when compared with Cur-dispersion.