目的 冬凌草甲素水溶性差,生物半衰期短,生物利用度低,制备冬凌草甲素立方液晶纳米粒,提高其溶解度,延长药物作用时间。方法 以新型液晶材料植烷三醇,结合丙二醇-泊洛沙姆407-水为体系,在1.2×105 kPa高压均质9次条件下,制备植烷三醇立方液晶纳米粒。利用偏光显微镜、小角X射线散射、冷冻透射电镜等对其进行表征。结果 测得纳米粒的平均粒径为(225.9±5.6)nm,平均电位为(-14.0±2.1)mV,包封率为(86.6±1.5)%,载药量为(3.69±0.06)mg·g-1,冬凌草甲素的溶解度提高了5.2倍,小角X射线散射证实立方液晶纳米粒为双菱形晶格结构(Pn3m)。释药模型拟合结果表明,体外释放曲线符合Higuchi方程,y=16.945 0t0.5+2.484 0(r2=0.997 2)。结论 制备的立方液晶纳米粒释放机制以扩散为主,能持续缓释24 h。
Abstract
OBJECTIVE To prepare oridonin-loaded cubosomes, and encapsulate oridonin(ORI) for the purpose of enhancing the solubility and prolonging the action time. METHODS Phytantriol (PYT) was firstly used to cooperate with Poloxamer 407-propylene glycol-water system to improve the solubility of ORI for developing ORI-loaded cubosomes. Polarizing microscope, small angel X-ray scattering (SAXS) and cryogenic transmission electron microscopy(cryo-TEM) were used to study the characters of cubosomes. RESULTS Under homogenization conditions of 1 200 bar for 9 cycles, the obtained PYT-based cubosomes had narrow particle size distribution with a mean particle size of (225.9±5.6) nm. The internal structures of cubosomes were revealed by small-angle X-ray scattering as a bicontinuous cubic liquid crystalline phase with Pn3m geometry. The encapsulation efficiency and drug loading determined by ultrafiltration centrifugation were (86.6±1.5)% and (3.69±0.06)mg·g-1, the solubility of ORI had been increased by 5.20 times. CONCLUSION The optimized formulas of cubosomes show obvious 24 h-sustained release, and the in vitro release profiles fitt the Higuchi release model well, implying diffusion-control as main release mechanism.
关键词
冬凌草甲素 /
立方液晶纳米粒 /
植烷三醇 /
增溶缓释
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Key words
oridonin /
cubosome /
phytantriol /
solubilization /
sustained release
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中图分类号：
R944
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参考文献
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