Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
J Pharm Sci. 2012 Jul;101(7):2382-91. doi: 10.1002/jps.23137. Epub 2012 Apr 4.
The biodegradable poly(organophosphazene) hydrogels were developed as a locally injectable drug carrier for a hydrophobic silibinin to overcome its limited bioavailability. The aqueous solution of poly(organophosphazene) enhanced the solubility of silibinin up to 2000 times compared with that of phosphate buffered saline (0.0415 vs. 84.55 mg/mL). Both aqueous polymer solutions with and without silibinin showed a sol-gel transition as a function of temperature. A faster in vitro degradation rate of the gel and drug release rate from the gel at pH 6.8 than those at pH 7.4 were observed when the degradation and release study on hydrogels were conducted at 37 °C. Silibinin was sustainedly released from the hydrogel mainly by a diffusion-controlled mechanism. The silibinin released from the hydrogel was shown to be effective considering the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In the HT-29 xenografted mice model, the intratumorally injected hydrogel containing silibinin exhibited a good antitumor effect in comparison with the control groups. The Western blotting indicated that one of the reasons for the enhanced antitumor effect of the hydrogel system was the sustained antiangiogenic effect of silibinin. The poly(organophosphazene) gels are expected to be an effective candidate of the locally injectable drug carrier for silibinin.
可生物降解的聚（有机磷腈）水凝胶被开发为一种局部可注射的药物载体，用于疏水性水飞蓟宾，以克服其有限的生物利用度。与磷酸盐缓冲盐水（0.0415 与 84.55mg/mL）相比，聚（有机磷腈）的水溶液将水飞蓟宾的溶解度提高了 2000 倍。含有和不含有水飞蓟宾的水聚合物溶液均表现出随温度的溶胶-凝胶转变。当在 37°C 下进行水凝胶的降解和释放研究时，观察到凝胶的体外降解速度更快，在 pH 6.8 时凝胶的药物释放速度比在 pH 7.4 时更快。水凝胶中的水飞蓟宾主要通过扩散控制机制持续释放。从水凝胶中释放的水飞蓟宾被证明是有效的，考虑到 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定。在 HT-29 异种移植小鼠模型中，与对照组相比，瘤内注射含有水飞蓟宾的水凝胶表现出良好的抗肿瘤效果。Western blotting 表明，水凝胶系统增强抗肿瘤作用的原因之一是水飞蓟宾的持续抗血管生成作用。聚（有机磷腈）凝胶有望成为局部可注射水飞蓟宾药物载体的有效候选物。
