Development and in vivo/in vitro evaluation of novel herpetrione nanosuspension
Development and in vivo/in vitro evaluation of novel herpetrione nanosuspension
复制标题
新型蛇皮酮纳米混悬剂的研制及体内/体外评价
DOI：
10.1016/j.ijpharm.2012.11.039
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发表时间：
2013-01-30
影响因子：
5.8
通讯作者：
Yuan, Hai-Long
中科院分区：
文献类型：
--
作者：
Guo, Jing-jing;Yue, Peng-Fei;Yuan, Hai-Long
Herpetrione （HPE）是一种从蜈蚣草中提取的新化合物，是一种新型有效的抗病毒药物。但由于水溶性较差，口服生物利用度较低。为了提高药物的溶出和吸收，本研究将HPE作为纳米混悬液进行了制备。采用高压均质法制备HPE纳米悬浮液，经冻干转化为干粉。然后利用光子相关光谱（PCS）、zeta电位测量、SEM和PXRD对纳米悬浮液进行了研究。为了验证减小粒径和增加表面积的理论假设，研究了体外溶出特性和体内药代动力学。研究了HPE纳米混悬液对2.2.15细胞HBsAg、HBeAg和HBV-DNA的抑制作用。结果表明，该纳米悬浮液的平均粒径为286 +/- 1.3 nm，多分散性指数为0.18 +/- 0.06，zeta电位为-26.9 +/- 2.4 mV。PXRD结果表明，HPE在粗粉和纳米悬浮液中均呈无定形。体外溶出试验中，HPE纳米混悬液的溶出速度明显提高。在体内评估中，与粗HPE相比，纳米混悬液的AUC（0-t）、C-max显著增加，T-max、MRT显著降低。HPE纳米混悬液对2.2.15细胞HBsAg、HBeAg和HBV-DNA的抑制作用强于HPE。体外活性实验证明，与粗混悬液相比，HPE纳米混悬液的功效有所增强。上述结果表明，纳米混悬液可以提高HPE在胃肠道的溶出速度和吸收，可能是口服给药HPE等生物利用度较差的药物的良好选择。(C) 2012 Elsevier b.v.版权所有
Herpetrione (HPE), is a new compound extracted from Herpetospermum caudigerum, which is proved to be a novel and potent antiviral agent. However, due to poor water solubility, oral bioavailability of the drug was relatively low. To improve the dissolution and absorption of the drug, formulation of HPE as nanosuspension has been performed in this study. HPE nanosuspension were produced by high pressure homogenization and transformed into dry powder by lyophilization. The nanosuspension was then investigated using photon correlation spectroscopy (PCS), zeta potential measurement, SEM and PXRD. To verify the theoretical hypothesis on the benefit of decreased particle size and increased surface area, in vitro dissolution characterization and in vivo pharmacokinetics were investigated. The inhibitory effect on HBsAg, HBeAg, and HBV-DNA of HPE nanosuspension in 2.2.15 cells was studied. Results showed that a narrow size distributed nanosuspension with a mean particle size of 286 +/- 1.3 nm, a polydispersity index of 0.18 +/- 0.06 and a zeta potential of -26.9 +/- 2.4 mV was obtained. The result of PXRD showed that HPE was amorphous state in both coarse powder and nanosuspension. In the in vitro dissolution test, HPE nanosuspension showed an increased dissolution velocity markedly. In the in vivo evaluation, compared to coarse HPE, nanosuspension exhibited significant increase in AUC(0-t), C-max and decrease in T-max, MRT. The inhibitory effect of HBsAg, HBeAg, and HBV-DNA of 2.2.15 cells treated by HPE nanosuspension were stronger than those of the HPE. The in vitro activity experiments provided evidence for an enhanced efficacy of the HPE nanosuspension formulation compared to HPE coarse suspension. These results revealed that particle size reduction could enhance HPE dissolution rate and absorption in gastrointestinal tract, and nanosuspension might be a good choice for oral delivery of poor bioavailability drug like HPE. (C) 2012 Elsevier B. V. All rights reserved.