Lan Li, Tian Fu-Rong, ZhuGe De-Li, ZhuGe Qi-Chuan, Shen Bi-Xin, Jin Bing-Hui, Huang Jian-Ping, Wu Ming-Ze, Fan Lu-Xin, Zhao Ying-Zheng, Xu He-Lin
Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province, China.
PLoS One. 2017 Mar 14;12(3):e0173814. doi: 10.1371/journal.pone.0173814. eCollection 2017.
In this study, porous gelatin microspheres (GMSs) were constructed to improve the neuroprotective effect of basic fibroblast growth factor (bFGF) on spinal cord injury. GMSs were prepared by a W/O emulsion template, followed by cross-linking, washing and drying. The particle sizes and surface porosity of the blank GMSs were carefully characterized by scan electronic microscopy. The blank GMSs have a mean particle size of 35μm and theirs surface was coarse and porous. bFGF was easily encapsulated inside the bulk GMSs through diffusion along the porous channel. 200μg of bFGF was completely encapsulated in 100mg of GMSs. The bFGF-loaded GMSs displayed a continuous drug release pattern without an obvious burst release over two weeks in vitro. Moreover, the therapeutic effects of bFGF-loaded GMSs were also evaluated in spinal cord injury rat model. After implantation of bFGF-loaded GMSs, the recovery of the motor function of SCI rats were evaluated by behavioral score and foot print experiment. The motor function of SCI rats treated with bFGF-loaded GMSs was more obvious than that treated with free bFGF solution (P<0.05). At the 28th days after treatment, rats were sacrificed and the injured spinal were removed for histopathological and apoptosis examination. Compared with treatment with free bFGF solution, treatment with bFGF-loaded GMSs resulted in a less necrosis, less infiltration of leukocytes, and a reduced the cavity ratio and less apoptotic cells in injured spinal(P<0.01), indicating its better therapeutic effect. Implantable porous GMSs may be a potential carrier to deliver bFGF for therapy of spinal cord injury.
在本研究中，构建了多孔明胶微球（GMSs）以提高碱性成纤维细胞生长因子（bFGF）对脊髓损伤的神经保护作用。通过W/O乳液模板制备GMSs，然后进行交联、洗涤和干燥。通过扫描电子显微镜仔细表征空白GMSs的粒径和表面孔隙率。空白GMSs的平均粒径为35μm，其表面粗糙且多孔。bFGF通过沿多孔通道的扩散很容易被包裹在大量GMSs内部。200μg的bFGF被完全包裹在100mg的GMSs中。负载bFGF的GMSs在体外两周内呈现持续的药物释放模式，没有明显的突释现象。此外，还在脊髓损伤大鼠模型中评估了负载bFGF的GMSs的治疗效果。植入负载bFGF的GMSs后，通过行为评分和足迹实验评估脊髓损伤大鼠的运动功能恢复情况。用负载bFGF的GMSs治疗的脊髓损伤大鼠的运动功能比用游离bFGF溶液治疗的更明显（P<0.05）。治疗后第28天，处死大鼠并取出损伤的脊髓进行组织病理学和凋亡检查。与用游离bFGF溶液治疗相比，用负载bFGF的GMSs治疗导致损伤脊髓中的坏死减少、白细胞浸润减少、空洞率降低且凋亡细胞减少（P<0.01），表明其治疗效果更好。可植入的多孔GMSs可能是递送bFGF用于治疗脊髓损伤的潜在载体。
