Preparation of hesperetin-polyvinylpyrrolidone sub-microparticles by supercritical anti-solvent technique for improved anti-cancer efficiency

The poor water solubility of hesperetin (HST) has impeded its relevant medical applications. To address this problem, the supercritical anti-solvent (SAS) technique was used to prepare HST-polyvinylpyrrolidone (HSTPVP) sub-microparticles. Additionally, the Box-Behnken Design was used to optimize three parameters (temperature, total solute concentration, and pressure) to determine the optimal process conditions, which were determined to be 40 degrees C, 5 mg/mL, and 100 bar. The physicochemical properties, drug release, and in vitro anticancer efficacy of the designed particles under the optimal conditions were systematically investigated. The drug loading of HST in HST-PVP sub-microparticles was quantified at 12.73 %. The dissolution rate of SAS-treated HST-PVP sub-microparticles was significantly enhanced compared to that of pure HST, leading to a higher anti-cancer efficiency of the HST-PVP sub-microparticles than that of pure HST. These findings indicate that the SAS technique holds significant potential for enhancing the bioavailability of hydrophobic drugs.