冰片/RGD双修饰多烯紫杉醇纳米粒经鼻给药抗脑胶质瘤作用研究  

The anti-glioma effects of borneol and RGD co-modified docetaxel loaded nanoparticles after intranasal administration

作　　者：赵霄 余双文 杜俊锋 倪淑婷 胡凯莉 ZHAO Xiao;YU Shuang-wen;DU Jun-feng;NI Shu-ting;HU Kai-li(Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Innovation Center of TCM Health Service,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学交叉科学研究院,上海201203 [2]上海中医药大学,上海中医健康服务协同创新中心,上海201203

出　　处：《药学学报》2021年第12期3233-3242,共10页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81773909);上海市科委启明星计划资助项目(13QA1403400)。

摘　　要：构建冰片(borneol,Bo)/RGD(Arg-Gly-Asp)双修饰载多烯紫杉醇(docetaxel,DTX)经鼻给药纳米靶向系统(DTX-Bo-RGD-NPs),提高DTX抗脑胶质瘤的治疗效果。采用乳化-溶媒挥发法制备DTX-Bo-RGD-NPs,考察其形态、粒径、zeta电位、载药量、稳定性及体外释放行为;采用包载coumarin-6荧光探针的纳米粒,考察C6和16HBE细胞对不同修饰纳米粒的摄取,评价体外靶向性;建立大鼠原位脑胶质瘤模型,鼻腔给予载DiR的纳米粒后,通过小动物活体成像观察脑肿瘤部位的荧光强度,评价其体内靶向性,并进行DTX-Bo-RGD-NPs抗大鼠原位脑胶质瘤的药效学研究。动物福利和实验过程均遵循上海中医药大学动物伦理委员会的规定。结果显示DTX-Bo-RGD-NPs形态圆整、大小均一,粒径在140 nm左右,zeta电位在-20~-30 mV,具有较好的体外粒径稳定性和缓释特性。体内和体外研究结果表明DTX-Bo-RGD-NPs具有良好的脑肿瘤靶向效果。新型脑部靶向递药系统DTX-Bo-RGD-NPs能有效提高经鼻给药后纳米粒的脑肿瘤靶向性能,增加其在肿瘤部位的聚集,提高DTX的抗脑胶质瘤治疗效果。Borneol(Bo)and Arg-Gly-Asp(RGD)co-modified docetaxel(DTX)loaded MPEG-PLGA nanoparticles(DTX-Bo-RGD-NPs)were prepared to improve the therapeutic effect of DTX against glioma after intranasal administration.DTX-Bo-RGD-NPs were prepared by emulsification-solvent evaporation method,and their morphology,particle size,zeta potential,drug loading capacity(DLC),stability,and in vitro release properties were investigated.The fluorescence probe coumarin-6 loaded NPs were prepared for investigating the NPs’uptake property on C6 and 16 HBE cell models to evaluate in vitro targeting ability.The DiR loaded NPs were prepared for observing the fluorescence intensity at the brain tumor site after intranasal administration through in vivo imaging system in a C6 rat orthotropic model,evaluating the targeting ability in vivo.The anti-tumor effects of DTX-BoRGD-NPs were also investigated in such C6 rat orthotropic model in vivo.Animal welfare and experimental procedures are in compliance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine.The results showed that DTX-Bo-RGD-NPs were spherical and uniformly distributed,with a particle size of about 140 nm and a zeta potential of-20 to-30 mV.The drug delivery system showed good stability and sustained release property in vitro,and favorable brain tumor targeting effect in vitro and in vivo.Such novel drug delivery system significantly improved the accumulation of DTX-Bo-RGD-NPs in tumor sites and displayed a higher brain tumor targeting efficiency,providing promising therapeutics of DTX for the treatment of glioma after intranasal administration.

关 键 词：脑胶质瘤 鼻腔给药 纳米粒 冰片 RGD肽 多烯紫杉醇 

分 类 号：R943[医药卫生—药剂学]