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

Abstract

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 (HST-PVP) 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 ℃, 5 mg/mL, and 100 bar. The physicochemical properties, drug release, and in vitro anti-cancer 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.