Abstract
Hesperetin (HST) is a bioflavonoid from citrus fruits and its clinical application is still markedly limited by its poor water solubility (1.27 µg/mL). Herein, a complex nanoparticle containing HST and hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared through supercritical antisolvent (SAS) technology to improve HST solubility, dissolution rate and bioactivity. The effects of crystallization temperature, crystallization pressure, mass flow rate, and drug concentration were systematically investigated using single-factor experiment and orthogonal experiment. The physicochemical properties and structure of the complex were examined using SEM, FTIR, DSC, BET, XPS and XRD analyses. After processing through SAS technology, the in vitro performance of HST was significantly improved such as solubility, dissolution rate and antineoplastic activity. HST as a potential antiproliferative and antioxidant compound appear to have anti-tumor effect on A549 cells. The above results proved that supercritical antisolvents crystallization was a feasible method to fabricate polymer-pharmaceutical complex nanoparticles for drug delivery system.
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