Qi Na, Cai Cuifang, Zhang Wei, Niu Yantao, Yang Jingyu, Wang Lihui, Tian Bin, Liu Xiaona, Lin Xia, Zhang Yu, Zhang Yan, He Haibing, Chen Kang, Tang Xing
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Department of Pharmaceutics, Guilin Medical University, Guilin 541004, PR China.
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Int J Pharm. 2014 Sep 10;472(1-2):48-55. doi: 10.1016/j.ijpharm.2014.06.005. Epub 2014 Jun 7.
This study described the development of vesicular phospholipid gels (VPGs) for sustained delivery of cytarabine (Ara-C) for the treatment of xenografted glioma. Ara-C-loaded VPGs in the state of a semisolid phospholipid dispersion looked like numerous vesicles tightly packing together under the freeze-fracture electron microscopy (FF-TEM), their release profiles displayed sustained drug release up to 384 h in vitro. The biodistribution of Ara-C in the rat brain showed that Ara-C-loaded VPGs could maintain therapeutic concentrations up to 5mm distance from the implantation site in brain tissue within 28 days. At the same time, fluorescence micrograph confirmed drug distribution in brain tissue visually. Furthermore, after single administration, Ara-C-loaded VPGs group significantly inhibited the U87-MG glioma growth in right flank in comparison with Ara-C solution (p<0.01). It was explained that the entrapped drug in VPGs could avoid degradation from cytidine deaminase and sustained release of drug from Ara-C-loaded VPGs could maintain the effective therapeutic levels for a long time around the tumor. In conclusion, Ara-C-loaded VPGs, with the properties of sustained release, high penetration capacity, nontoxicity and no shape restriction of the surgical cavity, are promising local delivery systems for post-surgical sustained chemotherapy against glioma.
本研究描述了用于阿糖胞苷（Ara-C）持续递送以治疗异种移植胶质瘤的囊泡磷脂凝胶（VPG）的开发。在冷冻断裂电子显微镜（FF-TEM）下，处于半固体磷脂分散状态的载Ara-C的VPG看起来像大量紧密堆积在一起的囊泡，其释放曲线显示在体外长达384小时的持续药物释放。Ara-C在大鼠脑中的生物分布表明，载Ara-C的VPG在28天内可在脑组织中距植入部位5mm的距离内维持治疗浓度。同时，荧光显微镜照片直观地证实了药物在脑组织中的分布。此外，单次给药后，与Ara-C溶液相比，载Ara-C的VPG组显著抑制了右侧腹U87-MG胶质瘤的生长（p<0.01）。这可以解释为VPG中包裹的药物可避免被胞苷脱氨酶降解，并且载Ara-C的VPG中药物的持续释放可在肿瘤周围长时间维持有效的治疗水平。总之，载Ara-C的VPG具有持续释放、高渗透能力、无毒且不受手术腔形状限制的特性，是用于胶质瘤术后持续化疗的有前景的局部递送系统。
