β-环糊精-大豆苷元/PEG_(20000)/Carbomer_(940)纳米晶的制备及体外性质评价

Preparation and in vitro property evaluation ofβ-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940)nanocrystals

通过与β-环糊精形成包合物,将其包埋在PEG_(20000)/Carbomer_(940)纳米晶体中,提高大豆苷元的溶解度和生物利用度。以大豆苷元为阳性药。分别以PEG_(20000)、Carbomer_(940)和NaOH作为增塑剂、胶凝剂和交联剂制备纳米晶体。采用两步法将不溶性药物大豆苷元包裹在β-CD中形成包合物,再包封在PEG_(20000)/Carbomer_(940)纳米晶中,形成β-环糊精-大豆苷元/PEG_(20000)/Carbomer_(940)纳米晶。以药物释放速率、再分散性、SEM形貌、包封率和载药量为指标,确定NaOH的最佳质量分数比为0.8%。通过傅里叶红外光谱(FTIR)、热重分析(TGA)和X射线衍射(XRD)分析确定了大豆苷元纳米晶体的包合状态,验证了制备的可行性;结果所制备的大豆苷元纳米晶体的平均Zeta电位分别为(-30.77±0.15)、(-37.47±0.64)mV;负载包合物的纳米晶体粒径分别为(333.60±3.81)、(544.60±7.66)nm;扫描电镜观察了大豆苷元载入前后纳米晶体的不规则分布;再分散实验表明,纳米晶体具有良好的分散效率;大豆苷元纳米晶在肠液pH中的体外溶出速度明显快于大豆苷元,且符合一级药物释放动力学模型;采用XRD、FT-IR和TGA等方法对载药前后大豆苷元纳米晶的多晶性质、载药量和热稳定性进行了测定;载入大豆苷元后的纳米晶由于大豆苷元明显抑菌作用,研究结果显示大豆苷元纳米晶较大豆苷元由于溶解度提高,对金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌抑制效果更加显著。大豆苷元纳米晶可显著提高难溶性药物大豆苷元的溶出度,提高其口服生物利用度。

This study aims to improve the solubility and bioavailability of daidzein by preparing theβ-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940)nanocrystals.Specifically,the nanocrystals were prepared with daidzein as a model drug,PEG_(20000),Carbomer_(940),and NaOH as a plasticizer,a gelling agent,and a crosslinking agent,respectively.A two-step method was employed to prepare theβ-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940)nanocystals.First,the insoluble drug daidzein was embedded inβ-cyclodextrin to form inclusion complexes,which were then encapsulated in the PEG_(20000)/Carbomer_(940)nanocrystals.The optimal mass fraction of NaOH was determined as 0.8%by the drug release rate,redispersability,SEM morphology,encapsulation rate,and drug loading.The inclusion status of daidzein nanocrystals was determined by Fourier transform infrared spectroscopy(FTIR),thermogravimetric analysis(TGA),and X-ray diffraction(XRD)analysis to verify the feasibility of the preparation.The prepared nanocrystals showed the average Zeta potential of(-30.77±0.15)mV and(-37.47±0.64)mV and the particle sizes of(333.60±3.81)nm and(544.60±7.66)nm before and after daidzein loading,respectively.The irregular distribution of nanocrystals before and after daidzein loading was observed under SEM.The redispersability experiment showed high dispersion efficiency of the nanocrystals.The in vitro dissolution rate of nanocrystals in intestinal fluid was significantly faster than that of daidzein,and followed the first-order drug release kinetic model.XRD,FTIR,and TGA were employed to determine the polycrystalline properties,drug loading,and thermal stability of the nanocrystals before and after drug loading.The nanocrystals loaded with daidzein demonstrated obvious antibacterial effect.The nanocrystals had more significant inhibitory effects on Staphylococcus aureus,Escherichia coli,and Pseudomonas aeruginosa than daidzein because of the improved solubility of daidzein.The prepared nanocrystals can significantly increase the dissolution rate and oral bioavailability of the insoluble drug daidzein.