赤芍总苷纳米混悬剂的制备、表征及药动学评价

摘要

Total paeony glycoside (TPG) is obtained from Radix Paeoniae Rubra with a variety of bioactivities.However,the low solubility and bioavailability limit its application.The present study aimed to develop TPG nanocrystals to increase the dissolution and then improve the oral bioavailability.TPG nanocrystals were prepared via precipitation and high-pressure homogenization method.The physical-chemical properties of the optimal TPG nanocrystals in terms of particle size,zeta potential,morphology and crystallinity were evaluated.The results showed that TPG nanocrystals had a mean particle size of(210.2±2.5) nm,a polydispersity index of 0.191±0.033 and a zeta potential of (-22.4±1.2) inV.The result of differential scanning calorimetry showed that the nanocrystals were still in crystalline state after the preparation procedure.Transmission electron microscopy (TEM) results showed that the nanosuspension was in spherical shape.The pharmacokinetics of TPG nanocrystals for rats was investigated by liquid chromatography-tandem mass spectroscopy (LC-MS/MS).Compared with the TPG coarse suspension,TPG nanocrystals exhibited significant increase in A UC0-∞ (approximately 1.85-fold).Taken together,TPG nanocrystals could be used as a promising drug delivery system due to the enhanced oral bioavailability of TPG.%赤芍总苷是从赤芍中得到的有效部位,它具有许多的生物学活性.然而,由于其溶解性差,生物利用度也非常低,使其应用受到限制.本研究将赤芍总苷制备成纳米混悬剂以增加溶解度,提高其口服生物利用度.采用沉淀-高压均质法制备赤芍总苷纳米混悬剂.用动态光散射法(DLS)测定其粒径、Zeta电位分别为(210.2±2.5) nm,(-22.4±1.2) mV.差示扫描量热图(DSC)结果显示,TPG在混悬剂中呈晶体状态,晶型并未改变.透射电镜(TEM)结果表明赤芍总苷纳米混悬剂呈球状晶体.采用液相色谱串联质谱法(LC-MS/MS)测定赤芍总苷纳米混悬剂在大鼠体内药物动力学参数,与赤芍总苷混悬液组药物动力学数据相比,AUC0-∞明显增大(约1.85倍),表明赤芍总苷纳米混悬剂可以提高赤芍总苷的生物利用度,是一种很有前景的给药体系.