叶酸修饰长春新碱介孔二氧化硅脂质纳米粒的制备及体外释药研究

Preparation and in vitro Release of Vincristine-loaded Phospholipid-capped Mesoporous Silica Nanoparticles Modified with Folic Acid as Targeting Drug Delivery System

目的:制备叶酸修饰长春新碱介孔二氧化硅脂质纳米粒(FA-VCR-MSNs-LP),对纳米粒进行质量评价并考察体外释药特性。方法:一步合成法制备氨基改性介孔二氧化硅纳米粒(NH2-MSNs),浸渍吸附法载入长春新碱(VCR),乙醇注入法制备叶酸修饰长春新碱介孔二氧化硅脂质纳米给药系统。利用透射电镜、小角粉末衍射仪、氮气吸脱附仪、红外光谱仪、激光粒度仪等考察其理化性质;高速离心法结合高效液相色谱(HPLC)测定其包封率及载药量;选用PBS(pH 7.4)作为释放介质,透析袋法考察其体外释药特性。结果:制备的FA-VCR-MSNs-LP透射电镜下外观呈圆形或类圆形,平均粒径为(178.5±8.5)nm,Zeta电位为(20.3±1.20)mV,包封率和载药量分别为(44.58±1.01)%(n=3)、(11.71±0.26)%(n=3);脂质修饰包裹后改善介孔二氧化硅纳米给药系统的突释现象,并具有缓释特征。结论:制备的FA-VCR-MSNs-LP性质稳定,包封率和载药量较高、粒径较小,体外释药具有明显缓释特征,为后期肿瘤靶向性和毒性研究奠定基础。

Objective: To prepare vincristine( VCR)-loaded phospholipid-capped mesoporous silica nanoparticles modified with folic acid( FA-VCR-MSNs-LP) and to investigate their physicochemical properties and in vitro release behavior. Methods: Amino group functionalized mesoporous silica nanoparticles( NH2-MSNs) were prepared by one-step synthesis method and VCR was loaded into them by solution adsorption. FA-VCR-MSNs-LP was developed by ethanol injection method. Transmission electron microscope,small angle X-ray diffraction,nitrogen adsorption,fourier transform infrared spectra and laser particle size analyzer were used to determine the physicochemical properties. The entrapment efficiency( EE) and drug loading( DL) were investigated with the method of high speed centrifugation combined with HPLC. The drug release behavior of FA-VCR-MSNs-LP was characterized with dynamic dialysis method using PBS( pH 7.4) as the release medium. Results: FA-VCR-MSNs-LP was spherical,and the mean particle size and zeta potential was( 178.5±8.5) nm and( 20.3±1.20) m V,respectively,and the EE and DL was( 44.58±1.01) % and( 11.71±0.26) %( n= 3),respectively.In vitro release behavior of FA-VCR-MSNs-LP improved the burst release at the first delivery stage of MSNs,and showed sustained-release characteristics. Conclusion: FA-VCR-MSNs-LP has stable physicochemical properties with small particle size,high EE and DL,and sustained-release behavior,which may lay a foundation for the study of tumor targeting and toxicity.