Enhanced cytotoxicity of osimertinib nanocrystals against lung cancer: Preparation, characterization and cytotoxicity studies against A549 cell lines

This work aimed to prepare osimertinib-loaded nanocrystals (OS-NCs) to enhance the cytotoxic effects against lung cancer cell lines (A549). Two batches of OS-NCs (NC1-NC2) were prepared by antisolvent precipitation followed by probe sonication technique using poloxamer-188 (PLX-188) as stabilizer. The developed nanocrystals were optimized based on particle size, polydispersity index (PDI) and zeta potential (ZP), DSC and FTIR. The NC2 was optimized with particle size (230 ± 18.5 nm), PDI (0.248) and ZP (−18.1 ± 1.99 mV). The optimized NC2 was further subjected for in-vitro release, stability studies, and MTT assay against A549 cell lines. Around seven-fold increase in solubility of OS from NC2 (7.01 mg mL⁻¹) was observed as compared to neat-OS (1.54 mg mL⁻¹), in phosphate buffer. In-vitro release of OS from NC2 was higher (98.6 %) as compared to neat-OS drug (73.6 %) at 12 h at pH 6.8. In-vitro cytotoxicity effects were examined on A549 cells. NC2 was found more potent to A549 cells compared with neat-OS with approximately less than half IC₅₀ value during MTT assay. The caspase-3, caspase-9, and p53 activities of NC2 demonstrated a remarkable cytotoxic effect against A549 lung cancer cells. These findings indicate that optimized NC2 show potential for enhancing delivery and effectiveness of OS for the treatment of lung cancer.