载芒果苷的氨基修饰介孔二氧化硅纳米粒的制备及口服药动学评价

Formulation optimization of mangiferin-amino-modified mesoporous silica nanoparticles and oral pharmacokinetics evaluation

目的优化芒果苷的氨基修饰介孔二氧化硅纳米粒(mangiferin-amino-modified mesoporous silica nanoparticles,MF-NH_(2)-MSNs)处方,并进行口服药动学评价。方法采用溶剂挥发法制备MF-NH_(2)-MSNs。单因素考察结合Box-Behnken设计-效应面法筛选MF-NH_(2)-MSNs处方,测定包封率、载药量、粒径、多分散指数(polydispersity index,PDI)和ζ电位。X粉末衍射法分析芒果苷在MF-NH_(2)-MSNs粉末中的存在状态,考察MF-NH_(2)-MSNs在模拟胃肠液中的释药行为,并拟合体外释药模型。SD大鼠ig给予MF-NH_(2)-MSNs粉末后采血,测定血药浓度,考察口服药动学行为并计算主要药动学参数。结果MF-NH_(2)-MSNs最佳处方为NH_(2)-MSNs与芒果苷比例1.7∶1,芒果苷质量浓度为0.54 mg/m L,搅拌时间为11.28 h。MF-NH_(2)-MSNs包封率为(92.34±1.04)%,载药量为(33.76±0.17)%,平均粒径为(204.18±8.66)nm,PDI值为0.120±0.014,ζ电位为(11.47±0.81)mV。芒果苷在MF-NH_(2)-MSNs粉末中以无定型状态存在,在模拟胃肠液中体外释药具有缓释特征,释药过程符合Weibull模型:lnln[1/(1-M_(t)/M_(∞))]=1.0320 lnt-1.625。口服药动学显示,MF-NH_(2)-MSNs半衰期(t_(1/2))增加至(4.19±0.87)h,血药浓度(C_(max))增加至(1506.77±404.80)ng/mL,相对口服生物利用度提高至4.02倍。结论MF-NH_(2)-MSNs增加了芒果苷累积释放度,显著促进口服吸收。

Objective To optimize prescriptions of mangiferin-amino-modified mesoporous silica nanoparticles(MF-NH_(2)-MSNs),and carry out oral pharmacokinetics evaluation.Methods Solvent evaporation method was employed to prepare MF-NH_(2)-MSNs.Single factor investigation combined with Box-Behnken response-surface design method was used to investigate the optimal prescriptions of MF-NH_(2)-MSNs.Entrapment efficiency,drug loading,particle size,PDI value andζpotential of MF-NH_(2)-MSNs were determined.Existence of mangiferin in MF-NH_(2)-MSNs powder was analyzed by X-ray powder diffraction(XRPD).In vitro release behavior of MF-NH_(2)-MSNs powder in simulated gastrointestinal fluid was also investigated,and the release model was fitted.SD rats were administered intragastrically of MF-NH_(2)-MSNs powder and blood samples were collected,oral pharmacokinetic behavior was investigated and the main pharmacokinetic parameters were calculated.Results Optimal prescriptions of MF-NH_(2)-MSNs:ratio of NH_(2)-MSNs to mangiferin was 1.7:1,concentration of mangiferin was 0.54 mg/mL and the stirring time was 11.28 h.Envelopment efficiency,drug loading,particle size,PDI value andζpotential were(92.34±1.04)%,(33.76±0.17)%,(204.18±8.66)nm,0.120±0.014 and(11.47±0.81)mV,respectively.Mangiferin existed in an amorphous state in MF-NH_(2)-MSNs powder.Drug release in vitro has obvious sustained-release characteristics in simulated gastrointestinal fluid,and release process conformed to Weibull model:lnln[1/(1-M_(t)/M_(∞))]=1.0320 lnt-1.625.The t_(1/2)of MF-NH_(2)-MSNs was increased to(4.19±0.87)h,C_(max)was enhanced to(1506.77±404.80)ng/mL and oral relative bioavailability of MF-NH_(2)-MSNs was increased to 4.02-fold.Conclusion MF-NH_(2)-MSNs increased the cumulative release of mangiferin and significantly promoted its oral absorption.