Angiopep-2修饰核-壳介孔二氧化硅脂质囊纳米粒的制备及体外评价

发布时间：2018-07-29 07:42

【摘要】：目的制备angiopep-2修饰核-壳结构介孔二氧化硅脂质囊纳米粒(ANG-MSN-LP),并进行体外评价。方法采用Stober法制备介孔二氧化硅纳米粒(MSN),改进了溶液吸附法来制备载紫杉醇(PTX)的介孔二氧化硅纳米粒(MSNPTX),然后以载紫杉醇的介孔二氧化硅纳米粒为核,运用自组装和薄膜水化法构建核-壳结构的angiopep-2修饰介孔二氧化硅脂质囊纳米粒(ANG-MSN-LP-PTX),透析袋法考察体外释药特性,噻唑蓝(MTT)法考察载体对人脑微毛细血管内皮细胞(HBMEC)和C6的细胞毒性,建立体外血脑屏障(BBB)模型研究载体对紫杉醇的跨膜转运能力和对C6细胞周期的影响。结果介孔二氧化硅纳米粒粒径为(94.61±3.91)nm[PDI(0.085±0.01)],比表面积(SBET)为425m2·g-1,孔容积(Vp)为0.37 cm3·g-1,孔径3.5 nm。介孔二氧化硅纳米粒在紫杉醇的饱和溶液中反复吸附7次时达到平衡,载药量高达11.1%。Angiopep-2修饰介孔二氧化硅脂质囊纳米粒分布均一,无团聚现象,具有明显的核-壳结构,粒径(106.37±3.76)nm[PDI(0.14±0.02)],并且在0~10μg·m L-1范围内对HBMEC和C6细胞具有良好的安全性和生物相容性。Angiopep-2修饰介孔二氧化硅脂质囊纳米粒体外释药48 h内的累积释放率达到75.5%,突释现象降低,具有明显的缓释特性;跨膜血脑屏障转运12 h后,对紫杉醇转运率高达10.74%;在细胞周期实验中,使C6细胞滞留在G2-M期细胞数比例为(40.92±6.20)%,显著高于各对照组数倍。结论 Angiopep-2修饰介孔二氧化硅脂质囊纳米粒是一种优良的递药载体并有望应用于脑胶质瘤的治疗;反复饱和溶液吸附法可有效提高药物载药量,值得应用和借鉴。
[Abstract]:Objective to prepare mesoporous silica lipid capsule nanoparticles (ANG-MSN-LP) modified by angiopep-2 and evaluate them in vitro. Methods mesoporous silica nanoparticles (MSN),) were prepared by Stober method. The solution adsorption method was improved to prepare mesoporous silica nanoparticles (MSNPTX),) loaded with paclitaxel (PTX) and then mesoporous silica nanoparticles loaded with paclitaxel (paclitaxel) were used as the core. Core-shell angiopep-2 modified mesoporous silica lipid capsule nanoparticles (ANG-MSN-LP-PTX) were constructed by self-assembly and membrane hydration. The release characteristics in vitro were investigated by dialysis bag method. The cytotoxicity of the carrier to (HBMEC) and C6 in human microcapillary endothelial cells was investigated by thiazolyl (MTT) assay. The effect of the vector on the transmembrane transport of paclitaxel and the cell cycle of C6 cells was studied by establishing the blood-brain barrier (BBB) model in vitro. Results the size of mesoporous silica nanoparticles was (94.61 卤3.91) nm [PDI (0.085 卤0.01)], the specific surface area (SBET) was 425m2 g-1, pore volume (Vp) was 0.37 cm3 g-1, pore size was 3.5nm. When the mesoporous silica nanoparticles were adsorbed repeatedly in the saturated solution of paclitaxel for 7 times, the drug loading was as high as that of 11.1%.Angiopep-2 modified mesoporous silica lipid capsules. The particle size was (106.37 卤3.76) nm [PDI (0.14 卤0.02)], and had good safety and biocompatibility for HBMEC and C6 cells in the range of 0 ~ 10 渭 g m ~ (-1). The cumulative release rate of Angiopep-2 modified mesoporous silica lipid capsule was 75.5 in vitro, and the sudden release was decreased. The rate of paclitaxel transport was as high as 10.74 after 12 h of transmembrane blood-brain barrier transport, and in the cell cycle experiment, the proportion of C6 cells in G2-M phase was (40.92 卤6.20), which was significantly higher than that in the control group (40.92 卤6.20). Conclusion Angiopep-2 modified mesoporous silica liposome nanoparticles is an excellent carrier for drug delivery and is expected to be used in the treatment of glioma. Repeated saturated solution adsorption method can effectively increase drug loading and is worthy of application and reference.
【作者单位】：浙江中医药大学药学院;
【基金】：国家自然科学基金资助项目(81274089;81473361) 浙江省自然科学基金资助项目(LZ13H280001)
【分类号】：R943

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