Abstract
Background: Gefitinib (Gef) is a first-line epidermal growth factor receptor (EGFR) inhibitor for NSCLC, but its clinical application is limited by poor aqueous solubility and low oral bioavailability. Methods: A self-assembled gefitinib nanosuspension (GG-NS) incorporating genistein (Gen) was rapidly developed and optimized via hammer acoustic resonance (HAR) technology. Systematic optimization was conducted using a high-throughput HAR-based process, with particle size, PDI, and zeta potential as key evaluation parameters. Structural and morphological characteristics were analyzed using powder X-ray diffraction (PXRD), thermal analysis, transmission electron microscopy (TEM), and Fourier-transform infrared (FT-IR) spectroscopy. In vitro dissolution behavior and cytotoxicity against A549 lung cancer cells were evaluated. Results: Optimal GG-NS with Z-Ave = 223.50 ± 1.53 nm, PDI = 0.239 ± 0.031 and zeta potential = -24.10 ± 0.47 mV was successfully prepared. The nanosuspension remained physically stable for up to five months at both 4 °C and 25 °C. Compared with the raw drugs, GG-NS enhanced the dissolution of gefitinib and genistein in water by 3.76-fold and 13-fold, respectively. In addition, GG-NS showed significantly enhanced cytotoxicity against A549 cells, with a 33.8% higher inhibition rate than the physical mixture after 72 h. Conclusions: This study demonstrates, for the first time, that HAR technology enables the rapid fabrication of a self-assembled GG-NS with improved dissolution performance, physicochemical stability, and in vitro anticancer activity, highlighting its promise as an efficient and scalable formulation strategy for poorly soluble anticancer drugs.