Despite significant advances in drug formulation, the clinical application of most active pharmaceutical ingredients from traditional Chinese herbs remained a significant challenge due to their poor solubility. To address this crucial issue, astragaloside-IV (AS-IV) was selected as a model drug to prepare nanoparticles with a large specific surface area via a constant, steady, and well-organized supercritical antisolvent (SAS) method. Initially, the optimal range of nanoparticle nucleation was determined by a single-factor investigation under altered critical conditions. Under the optimized conditions obtained from the Box-Behnken Design model analysis (AS-IV solution flow rate (F): 0.85 mL/min, Temperature (T): 42 ℃, Pressure (P): 120 bar), the SAS process resulted in nanospheres with smooth surface and narrow particle size distribution. After the SAS process treatment, AS-IV with altered physical states presented improved solubility and enhanced in vitro antiproliferative effects compared to untreated AS-IV, illustrating the potential application of the SAS method in promoting the bioavailability of low water-soluble drugs.

尽管在药物制剂方面取得了重大进展，但由于其溶解度差，大多数中药活性药物成分的临床应用仍然是一项重大挑战。为了解决这一关键问题，黄芪甲苷（AS-IV）被选为模型药物，通过恒定、稳定和组织良好的超临界反溶剂（SAS）方法制备具有大比表面积的纳米颗粒。最初，纳米粒子成核的最佳范围是通过在改变的临界条件下进行的单因素研究来确定的。在从 Box-Behnken 设计模型分析得到的优化条件下（AS-IV 溶液流速（F）：0.85 mL/min，温度（T）：42 ℃，压力（P): 120 bar)，SAS 工艺产生的纳米球表面光滑，粒径分布窄。经过 SAS 工艺处理后，与未经处理的 AS-IV 相比，物理状态改变的 AS-IV 表现出更高的溶解度和增强的体外抗增殖作用，说明了 SAS 方法在提高低水溶性药物生物利用度方面的潜在应用。