Xie Li-ya, Chang Di, Hou Zhen-qing, Yang Xiang-rui, Han Ding
Yao Xue Xue Bao. 2016 Aug;51(8):1309-15.
In this study, we used Shirasu porous glass membrane(SPG) as a template and hydroxy camptothecin (HCPT) as a model drug to prepare the comet-shaped Me PEG [methoxyl poly(ethylene glycol)]- PLGA [poly(lactic-co-glycolic acid)-HCPT amphiphilic block copolymer. Our method was optimized by the orthogonal design method. The partical size, zeta potential, drug-loaded content, yield, shape and status of the obtained comet-shaped Me PEG-PLGA-HCPT particles were further characterized by dynamic light scattering(DLS), scanning electron microscopy(SEM)/transmission electron microscopy (TEM), X-ray diffraction(XRD) and differential scanning calorimetry (DSC) et al, respectively. In vitro release was preliminary evaluated. MTT assay to preliminary evaluate the cytotoxicity of particles against human liver BEL-7402 cells. Based on these experimental results, the optimal preparation conditions contain: weight ratio of HCPT to Me PEG-PLGA was 1:1, nitrogen pressure was 100 k Pa and SPG membrane pore size was 1.1 μm. The particles exhibited a comet-shaped shape, fairly uniform size and were well dispersed. The drug-loading content was 46.2%, with yield of 96.4%, and zeta-31.4 m V. The distribution of HCPT in particles was very uniform, and HCPT showed a amorphous state existed in particles. The release behavior in vitro showed sustained releasing, and with the drug loading content in proportion to the release of the drug. MTT test indicated that the HCPT-loaded comet-shaped particles had enhanced the cytotoxicity against human liver BEL-7402 cells relatively to the HCPT-loaded spherical particles in vitro. The results showed a promising potential application of the preparation in clinical treatment of tumor.
在本研究中，我们以白榴石多孔玻璃膜（SPG）为模板，以羟基喜树碱（HCPT）为模型药物，制备了彗星状甲氧基聚乙二醇（Me PEG）-聚乳酸-羟基乙酸共聚物（PLGA）-HCPT两亲性嵌段共聚物。我们的方法采用正交设计法进行了优化。通过动态光散射（DLS）、扫描电子显微镜（SEM）/透射电子显微镜（TEM）、X射线衍射（XRD）和差示扫描量热法（DSC）等分别进一步表征了所得彗星状Me PEG-PLGA-HCPT颗粒的粒径、zeta电位、载药量、产率、形状和状态。对体外释放进行了初步评估。采用MTT法初步评估颗粒对人肝癌BEL-7402细胞的细胞毒性。基于这些实验结果，最佳制备条件为：HCPT与Me PEG-PLGA的重量比为1:1，氮气压力为100 kPa，SPG膜孔径为1.1μm。颗粒呈彗星状，尺寸相当均匀且分散良好。载药量为46.2%，产率为96.4%，zeta电位为-31.4 mV。HCPT在颗粒中的分布非常均匀，且HCPT在颗粒中呈无定形状态存在。体外释放行为显示为持续释放，且药物释放与载药量成正比。MTT试验表明，相对于体外加载HCPT的球形颗粒，加载HCPT的彗星状颗粒对人肝癌BEL-7402细胞的细胞毒性增强。结果表明该制剂在肿瘤临床治疗中具有广阔的潜在应用前景。
