Dong Qiannian, Yuan Hui-Ling, Qian Jia-Jia, Zhang Cai-Yun, Chen Wei-Dong
School of Pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine, Hefei 230038, P.R. China.
Biomed Mater Eng. 2018;29(3):333-345. doi: 10.3233/BME-181729.
Nanosuspensions technique is an important tool to enhance the saturation solubility and dissolution velocity of poorly soluble drugs. Trans-resveratrol (t-Res) with extensive pharmacological effects was severely restricted by poor solubility and short biological half-life. In this study, anti-solvent precipitation was employed to development trans-resveratrol nanosuspensions (t-Res NS) with PVPK30 as stabilizer. The physicochemical properties, in vitro release and in vivo pharmacokinetics of t-Res NS were investigated. The mean particle size, zeta potential, encapsulation efficiency and drug loading of t-Res NS prepared by the optimal prescription were 96.9 nm, -20.4mV, 78% and 28.1%, respectively. The morphology of t-Res nanoparticles was spherical indicated by SEM with amorphous phase verified by XRD and DSC. The t-Res NS present a good physical stability as well as enhanced chemical stability. Compared to crude drug, the in vitro dissolution rate of t-Res NS was increased with fitting Higuchi equation (Q=0.3215t1/2+0.0070). The in vivo pharmacokinetic test in rats showed that the AUC0∼t of t-Res NS (559.4 μg/mL·min) was about 3.6-fold higher than that of t-Res solution. Meanwhile, the MRT of t-Res nanosuspensions was longer than that of t-Res solution. These results suggested that NS may be a potentially nanocarrier for clinical delivery of t-Res.
纳米混悬液技术是提高难溶性药物饱和溶解度和溶解速度的重要工具。具有广泛药理作用的反式白藜芦醇(t-Res)因溶解度差和生物半衰期短而受到严重限制。本研究采用抗溶剂沉淀法,以PVPK30为稳定剂制备反式白藜芦醇纳米混悬液(t-Res NS)。考察了t-Res NS的理化性质、体外释放和体内药代动力学。优化处方制备的t-Res NS的平均粒径、zeta电位、包封率和载药量分别为96.9 nm、-20.4mV、78%和28.1%。扫描电镜显示t-Res纳米粒呈球形,X射线衍射和差示扫描量热法证实为非晶相。t-Res NS具有良好的物理稳定性和增强的化学稳定性。与原料药相比,t-Res NS的体外溶出速率增加,符合Higuchi方程(Q=0.3215t1/2+0.0070)。大鼠体内药代动力学试验表明,t-Res NS的AUC0∼t(559.4μg/mL·min)约为t-Res溶液的3.6倍。同时,t-Res纳米混悬液的平均滞留时间长于t-Res溶液。这些结果表明,纳米混悬液可能是t-Res临床给药的潜在纳米载体。