透明质酸功能化MCM-41型介孔二氧化硅包载紫杉醇纳米粒对体外SMMC-7721肝癌细胞作用研究
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摘要
目的构建透明质酸(hyaluronan hyaluronic acid,HA)功能化MCM-41型介孔二氧化硅纳米粒(MCM-41)包载紫杉醇(paclitaxel,PTX)的靶向药物递送系统(HA-MCM-41-PTX)。考察其理化性质、体外释药行为及体外肿瘤抑制效果。方法通过透射电镜考察MCM-41的形态结构及粒径,粉末X射线衍射法和傅里叶红外光谱法对载药体系进行表征,体外溶出实验考察载药体系的体外释放行为,体外细胞实验探究载药体系对SMMC-7721细胞的作用机制。结果 HA-MCM-41-PTX载药量为26. 75%。体外释药呈缓释,48 h药物累积释放量为(86. 19±5. 11)%。细胞实验表明,载药体系具有靶向作用,易被细胞摄入并表现出良好的肿瘤细胞抑制作用。结论 HA-MCM-41-PTX是同时具有缓释性和靶向性的载药体系。
OBJECTIVE To establish a drug delivery system based on hyaluronic acid functionalized mesoporous silica nanoparticles MCM-41 loaded with paclitaxel( HA-MCM-41-PTX). The physical and chemical properties,in vitro drug release and the antitumor effect were investigated. METHODS The morphological structure and particle size of MCM-41 were observed by TEM. The drug delivery system was characterized by PXRD and FTIR. The in vitro release experiments was carried out to investigate the dissolution rate of HA-MCM-41-PTX. The in vitro cells experiment was carried out to explore the mechanism of HA-MCM-41-PTX on cells. RESULTS The drug loading capacity of HA-MCM-41-PTX was 28. 75%. The in vitro drug release experiments showed that HA-MCM-41-PTX exhibited controlled release with a cumulative release of( 86. 19 ± 5. 11) % until 48 h. In vitro cell experiments showed that HA-MCM-41-PTX had excellent targeting effect due to the modification of hyaluronic acid,which was easier to be uptaken by cells and exhibited great antitumor effect. CONCLUSION HA-MCM-41-PTX is an excellent drug delivery system with both controlled release and targeting antitumor effect.
OBJECTIVE To establish a drug delivery system based on hyaluronic acid functionalized mesoporous silica nanoparticles MCM-41 loaded with paclitaxel( HA-MCM-41-PTX). The physical and chemical properties,in vitro drug release and the antitumor effect were investigated. METHODS The morphological structure and particle size of MCM-41 were observed by TEM. The drug delivery system was characterized by PXRD and FTIR. The in vitro release experiments was carried out to investigate the dissolution rate of HA-MCM-41-PTX. The in vitro cells experiment was carried out to explore the mechanism of HA-MCM-41-PTX on cells. RESULTS The drug loading capacity of HA-MCM-41-PTX was 28. 75%. The in vitro drug release experiments showed that HA-MCM-41-PTX exhibited controlled release with a cumulative release of( 86. 19 ± 5. 11) % until 48 h. In vitro cell experiments showed that HA-MCM-41-PTX had excellent targeting effect due to the modification of hyaluronic acid,which was easier to be uptaken by cells and exhibited great antitumor effect. CONCLUSION HA-MCM-41-PTX is an excellent drug delivery system with both controlled release and targeting antitumor effect.
引文
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[3] YANG X Y,SHI X Q,JI J B,et al. Development of redox-responsive theranostic nanoparticles for near-infrared fluorescence imaging-guided photodynamic/chemotherapy of tumor[J]. Drug Deliv,2018,25(1):780-796.
[4] ZHAO Q F,LIU J,ZHU W Q,et al. Dual-stimuli responsive hyaluronic acid-conjugated mesoporous silica for targeted delivery to CD44-overexpressing cancer cells[J]. Acta Biomater,2015,23:147-156.
[5] LU Y,LI Y,WU W. Injected nanocrystals for targeted drug delivery[J]. Acta Pharm Sin B(药学学报英文),2016,6(2):106-113.
[6] NAIRI V,MAGNOLIA S,PILUDU M,et al. Mesoporous silica nanoparticles functionalized with hyaluronic acid. Effect of the biopolymer chain length on cell internalization[J]. Colloids Surfaces B:Biointerfaces,2018,168(1):50-59.
[7] CHEN C,SUN W,WANG X L,et al. pH-responsive nanoreservoirs based on hyaluronic acid end-capped mesoporous silica nanoparticles for targeted drug deliver[J]. Int J Biolo Macromol,2018,111(5):1106-1115.
[8] MOHAOATRA S,ROUT S R,NARAYAN R,et al. Multifunctional mesoporous hollow silica nanocapsules for targeted co-delivery of cisplatin-pemetrexed and MR imaging[J]. Dalton Trans,2014,43(42):15841-15850.
[9] BI Y P,WU C N,XIN M,et al. Facile large-scale preparation of mesoporous silica microspheres with the assistance of sucrose and their drug loading and releasing properties[J]. Int J Pharm,2016,500(1-2):77-84.
[10] QU X Y,ZOU Y,HE C Y,et al. Improved intestinal absorption of paclitaxel by mixed micelles self-assembled from vitamin E succinate-based amphiphilic polymers and their transcellular transport mechanism and intracellular trafficking routes[J].Drug Deliv,2018,25(1):210-225.
[11] XU X Y,WU C,BAI A D,et al. Folate functionalized mesoporous silica nanoparticles as a liver tumor-targeted drug delivery system for improving the antitumor effect of paclitaxel[J]. J Nanomater,2017:1-13.
[12] WAN L,WANG X F,ZHU W Q,et al. Folate-polyethyleneimine functionalized mesoporous carbon nanoparticles for enhancing oral bioavailability of paclitaxel[J]. Int J Pharm,2015,484(1-2):207-217.
[13] LI J,MIAO X Q,CHEN T K,et al. Preparation and characterization of pelletized solid dispersion of resveratrol with mesoporous silica microparticles to improve dissolution by fluid-bed coating techniques[J]. Asian J Pharm Sci,2016,11(4):528-535.
[14] ZHANG J,SUN Y J,TIAN B C,et al. Multifunctional mesoporous silica nanoparticles modified with tumor-shedable hyaluronic acid as carriers for doxorubicin[J]. Colloids Surfaces B:Biointerfaces,2016,144(4):293-302.
[15] GHOSH S C,NESLIHAN A S,KLOSTERGAARD J. CD44:a validated target for improved delivery of cancer therapeutics[J].Expert Opin Ther Targets,2012,16(7):635-650.
[16] HUANG G L,HUANG H L. Application of hyaluronic acid as carriers in drug delivery[J]. Drug Deliv,2018,25(1):766-772.
[17] LV Y Q,XU C R,LIN C S,et al. Nanoplatform assembled from a CD44-targeted prodrug and smart liposomes for dual targeting of tumor microenvironment and and cancer cells[J]. ACS Nano,2018,12(2):1519-1536.
[18] JIANG H P,SHI X Y,YU X Y,et al. Hyaluronidase enzymeresponsive targeted nanoparticle for effective delivery of 5-fluorouracil in colon cancer[J]. Pharm Res,2018,35(4):73.
[19] ZHANG M Z,XU C L,WEN L Q,et al. A hyaluronidase responsive nanoparticle-based drug delivery system for targeting colon cancer cells[J]. Cancer Res,2016,76(24):7208-7218.