目的 制备异甘草素-玉米肽纳米复合物（isoliquiritigenin-corn peptide nanocomplexes，ISL-CP-NCs），考察理化性质及口服药动学行为。方法 分子模拟对接法探究异甘草素与玉米肽结合的相互作用。采用自组装法制备ISL-CP-NCs，Box-Behnken设计-效应面法优化ISL-CP-NCs处方。透射电子显微镜（transmission electron microscopy，TEM）观察ISL-CP-NCs形貌，X-射线粉末衍射法（X-ray powder diffraction，XRPD）分析异甘草素晶型，傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FTIR）分析研究异甘草素和玉米肽结合机制。测定ISL-CP-NCs饱和溶解度，透析袋法考察ISL-CP-NCs释药行为。SD大鼠分别ig给予异甘草素和ISL-CP-NCs，计算主要药动学参数及相对生物利用度。结果 ISL-CP-NCs最佳处方为甘草素质量浓度为8.90 mg/mL，玉米肽质量浓度为100.00 mg/mL，制备时间为2.25 h。ISL-CP-NCs包封率、载药量、粒径及ζ电位分别为（88.57±0.57）%、（7.37±0.11）%、（84.40±2.02）nm和（−21.84±0.80）mV，微观形貌为类球形。异甘草素可能与玉米肽之间发生了络合作用，并使异甘草素转变为无定形态。ISL-CP-NCs将异甘草素在纯化水、模拟胃、肠液中溶解度分别增加至233.41、309.61和213.48倍。ISL-CP-NCs在模拟胃、肠液中12 h累积释放度分别提高至83.83%和78.87%，释药行为符合Weibull模型。ISL-CP-NCs半衰期（t_1/2）延长至（4.23±1.61）h，达峰时间（t_max）延后至（2.17±0.56）h，达峰浓度（C_max）和相对口服吸收生物利用度分别提高至3.40倍和3.88倍。结论 ISL-CP-NCs显著增加了异甘草素的溶解度、释放度及相对生物利用度，为后续药效学研究奠定实验基础。

Objective To prepare isoliquiritigenin-corn peptide nanocomplexes (ISL-CP-NCs), and study its physicochemical properties and oral pharmacokinetics behavior. Methods Molecular simulation docking method was employed to investigate the binding interaction between isoliquiritigenin and corn peptide. Self-assembly method was used to prepare ISL-CP-NCs, Box-Behnken response surface design method (BBD-RSM) was employed to optimize prescriptions of ISL-CP-NCs. Transmission electron microscope (TEM) was employed to observe microscopic appearance of ISL-CP-NCs. X-ray powder diffraction (XRPD) was employed to analyze the crystal form of isoliquiritigenin in ISL-CP-NCs powder, Fourier transform infrared spectrometer (FTIR) was used to study binding mechanism of isoliquiritigenin and corn peptide. Determining the saturated solubility of ISL-CP-NCs, and studying the drug release behavior of ISL-CP-NCs by dialysis bag method. SD rats were administered intragastrically with isoliquiritigenin and ISL-CP-NCs respectively, and main pharmacokinetic parameters and relative bioavailability were also calculated. Results Optimal formulations of ISL-CP-NCs: mass concentration of isoliquiritigenin was 8.90 mg/mL, mass concentration of corn peptide was 100.00 mg/mL and prepare time was 2.25 h. Envelopment efficiency, drug loading, particle size and ζ potential were (88.57 ± 0.57)%, (7.37 ± 0.11)%, (84.40 ± 2.02) nm and (−21.84 ± 0.80) mV, respectively. Microscopic morphology of ISL-CP-NCs were spheroidal. Isoglycyrrhizin may have chelated with corn peptide and turned into an amorphous form in ISL-CP-NCs powder. ISL-CP-NCs increased the solubility of isoliquiritigenin in distilled water, simulated gastric fluids and intestinal fluids by 233.41, 309.61 and 213.48 times, respectively. Cumulative drug release of ISL-CP-NCs in simulated gastric and intestinal fluids increased to 83.83% and 78.87% in 12 h, and the drug release behavior was in accordance with Weibull model. The t_1/2 was prolonged to (4.23 ± 1.61) h, t_max of ISL-CP-NCs was postponed to (2.17 ± 0.56) h, C_max and relative oral bioavailability were increased to 3.40 and 3.88 times, respectively. Conclusion ISL-CP-NCs significantly increased the solubility, release rate and relative bioavailability of isoliquiritigenin, which laid an experimental foundation for subsequent pharmacodynamics research.

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河南省二〇二四年科技发展计划（242102230118）；山西省中央引导地方科技发展资金项目（YDZJSX2024B014）；山西省中医药科技创新工程项目（2023kjzy009）