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-NH₂-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-NH₂-MSNs。单因素考察结合Box-Behnken设计-效应面法筛选MF-NH₂-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-NH₂-MSNs粉末中的存在状态,考察MF-NH₂-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-NH₂-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-NH₂-MSNs最佳处方为NH₂-MSNs与芒果苷比例1.7:1,芒果苷质量浓度为0.54 mg/mL,搅拌时间为11.28 h。MF-NH₂-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-NH₂-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_∞)]=1.032 0 lnt-1.625。口服药动学显示,MF-NH₂-MSNs半衰期(t_1/2)增加至(4.19±0.87)h,血药浓度(C_max)增加至(1 506.77±404.80)ng/mL,相对口服生物利用度提高至4.02倍。结论 MF-NH₂-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-NH₂-MSNs), and carry out oral pharmacokinetics evaluation. Methods Solvent evaporation method was employed to prepare MF-NH₂-MSNs. Single factor investigation combined with Box-Behnken response-surface design method was used to investigate the optimal prescriptions of MF-NH₂-MSNs. Entrapment efficiency, drug loading, particle size, PDI value and ζ potential of MF-NH₂-MSNs were determined. Existence of mangiferin in MF-NH₂-MSNs powder was analyzed by X-ray powder diffraction (XRPD). In vitro release behavior of MF-NH₂-MSNs powder in simulated gastrointestinal fluid was also investigated, and the release model was fitted. SD rats were administered intragastrically of MF-NH₂-MSNs powder and blood samples were collected, oral pharmacokinetic behavior was investigated and the main pharmacokinetic parameters were calculated. Results Optimal prescriptions of MF-NH₂-MSNs:ratio of NH₂-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 and ζ potential 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-NH₂-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_∞)]=1.032 0 lnt-1.625. The t_1/2 of MF-NH₂-MSNs was increased to (4.19 ± 0.87) h, C_max was enhanced to (1 506.77 ± 404.80) ng/mL and oral relative bioavailability of MF-NH₂-MSNs was increased to 4.02-fold. Conclusion MF-NH₂-MSNs increased the cumulative release of mangiferin and significantly promoted its oral absorption.

河南省高等学校重点科研项目计划（23B320013）；河南应用技术职业学院“青年骨干教师”（2022-GGJS-H002）；河南应用技术职业学院“首席技师”（2022-SXJS-HL01）