Preparation of astragaloside IV (AS-IV) nanoparticles via SAS process for anticancer efficacy: Optimization based on Box-Behnken Design

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. • The BBD method is applied to optimize the experimental conditions of SAS process. • AS-IV particles with a mean size of 61.59 nm are obtained under optimized conditions. • SAS-based nanonized AS-IV presented improved anti-cancer efficacy.