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丝素蛋白作为药物缓释载体的研究进展
药物缓释体系有利于提高药物疗效、降低毒副作用,可减轻病人多次用药的痛苦,对于提高临床用药水平具有重大意义[1],是近年来国际范围内研究的热门的领域之一.在药物缓释体系中,除药物本身外,药物载体也扮演着重要角色,合成高分子载体常常生物相容性不好,有时还含有痕量引发剂等毒性杂质,例如在聚乳酸的一般生产方法中使用了有机锡催化剂,会产生细胞毒性[2].
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在胃肿瘤治疗中5-氟尿嘧啶聚乳酸纳米颗粒和微囊体的靶向性和控释性的研究
The aim of this paper was to evaluate controlled release behavior and the therapeutic efficacy of 5-FU-loaded Poly(lactic acid) (PLA)microspheres to human gastric cancer xenograft, and the targeting effect of VEGF/5-FU loaded PLA nanoparticles. 5-FU-loaded PLA microspheres were prepared by an emulsion evaporation method, and were characterized by scanning electron microscopy (SEM). 5-FU loaded PLA nanoparticles were characterized by (TEM), and particle size analyzer determined the distribution of nanoparticles size. The release performances of 5-FU microspheres in vitro were studied in PH 7.4 phosphate buffered saline. The therapeutic efficacy of 5-FU-loaded PLA microspheres in vivo were studied using MGC-803 (human stomach cancer) xenograft. 32 nude mice were divided into four groups (n =8), 5-FU loaded PLA microspheres were injected at tumor site. VEGF121monoclonal antibody was connected with 5-FU loaded PLA nanoparticles through carbodimide. The targeted effect of VEGF 5-FU loaded nanoparticles in vivo were observed by single photon emission computed tomography (SPECT)after tail vein injection at 1 h and 2 h. SEM observation showed that microspheres were spherical, and the diameters of two kinds of microspheres were 1 μm and 5 μm respectively. The mcan diameter of nanoparticles was 191.0 nm,and the index of polydispersity was 0.202. The drug was released following biphasic kinetics, initial burst and the following steady phase. 1 μm and 5 μm 5-FU-loaded microspheres both resulted in increased life span (1 μm microspheres median survival time=40.63 days, 5 μm microspheres median survival time=62.25 days), against 5-FU pure drug (median survival time=14.5 days). These results strongly suggest that 5-FU-loaded PLA microspheres increase life span of nude mice bearing MGC-803 tumors. After injection for 2 h, almost all the VEGF/5-FU loaded PLA nanoparticles could centralize at the human gastric cancer xenograft sites. That demonstrated VEGF monoclonal antibody remain its bioactivity after connection with nanoparticles, VEGF/5-FU loaded PLA nanoparticles had very exact targeting function for gastric tumor xenograft.
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高建青教授课题组在构建基于干细胞的新型生物类靶向传递系统的应用研究上取得新突破
2015年5月8日，浙江大学药学院药物制剂研究所高建青教授课题组在国际控释学会会刊《控释杂志》（ Journal of Controlled Release）在线发表了题为“Synergistic effects of co－administration of suicide gene expressing mesenchymal stem cells and prodrug－encapsulated liposome on aggressive lung melanoma metastases in mice”的研究论文（ http：／／www．sciencedirect ． com／science／article／pii／S0168365915003053）。该研究利用骨髓间充质干细胞的肿瘤归巢性质构建了具有生物活性的细胞载体传递系统，并联合脂质纳米载体进行共给药，实现了药物－基因的共靶向传递，并在小鼠恶性肺黑色素转移瘤模型上取得了良好的抑瘤效果。
