Li Xin, Yuan Huiling, Zhang Caiyun, Chen Weidong, Cheng Weiye, Chen Xin, Ye Xi
College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, China.
J Pharm Pharmacol. 2016 Aug;68(8):980-8. doi: 10.1111/jphp.12575. Epub 2016 Jun 10.
OBJECTIVES: We developed Cur nanosuspension (Cur-NS) with PVPK30 and SDS as stabilizers to improve poor water solubility and short biological half-time of Cur. METHODS: Physicochemical characterization of Cur-NS was characterized systematically. The in-vitro dissolution, cytotoxicity and in-vivo pharmacokinetic experiments of Cur-NS were also evaluated. KEY FINDINGS: Scanning electron microscope indicated that the morphologies of Cur-NS were spherical or ellipsoidal in shape. X-ray diffraction verified that Cur was successfully developed as nanoparticles with an amorphous phase in Cur-NS. Fourier transform infrared spectroscopy suggested there was no degradation about Cur in the Cur-NS. Furthermore, the in-vitro study showed that the cumulative release of the Cur-NS was 82.16 ± 2.62% within 34 h and the cytotoxicity of the Cur-NS against HepG2 cells was much better than raw Cur. Besides, in-vivo pharmacokinetics in rats by intravenous injection displayed that the in-vivo process of Cur-NS pertained to two-compartment model. Meanwhile, the t1/2 and AUC0-t of Cur-NS were enhanced by 11.0-fold and 4.2-fold comparing to Cur solution. CONCLUSIONS: The Cur-NS significantly increased the water solubility and half-time of Cur, suggesting its potential as a nanocarrier in the delivery of Cur for future clinical application.
目的:我们以聚乙烯吡咯烷酮K30(PVPK30)和十二烷基硫酸钠(SDS)作为稳定剂开发了姜黄素纳米混悬液(Cur-NS),以改善姜黄素水溶性差和生物半衰期短的问题。 方法:系统地表征了Cur-NS的理化性质。还评估了Cur-NS的体外溶出度、细胞毒性和体内药代动力学实验。 主要发现:扫描电子显微镜表明Cur-NS的形态为球形或椭圆形。X射线衍射证实Cur在Cur-NS中成功开发为具有非晶相的纳米颗粒。傅里叶变换红外光谱表明Cur-NS中的Cur没有降解。此外,体外研究表明,Cur-NS在34小时内的累积释放率为82.16±2.62%,Cur-NS对HepG2细胞的细胞毒性比原料药姜黄素要好得多。此外,大鼠静脉注射的体内药代动力学显示,Cur-NS的体内过程符合二室模型。同时,与姜黄素溶液相比,Cur-NS的t1/2和AUC0-t分别提高了11.0倍和4.2倍。 结论:Cur-NS显著提高了姜黄素的水溶性和半衰期,表明其作为姜黄素递送的纳米载体在未来临床应用中的潜力。
J Pharm Pharmacol. 2016-8
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