Synthesis and characterization of l-arginine-grafted chitosan nanoparticles for intranasal Dasatinib delivery and brain targeting.

Glioblastoma (GBM) remains a highly aggressive brain malignancy with limited therapeutic success owing to poor drug accumulation and restricted brain delivery. Dasatinib (DTB), a tyrosine kinase inhibitor with anticancer potential, is limited by poor solubility and brain penetration. This study developed l-arginine-grafted low-molecular-weight chitosan nanoparticles (DTB-LA-g-CS-NPs) for intranasal DTB delivery. CS-g-LA was synthesized by EDC/NHS-mediated coupling and characterized by FTIR, 1H NMR, XRD, and SEM. The optimized nanoparticles exhibited a particle size of 151.2 ± 3.4 nm, zeta potential of +31.6 ± 2.4 mV, and entrapment efficiency of 82.7 ± 1.8%. Drug release reached 95.2 ± 3.5% within 36 h, with cellular uptake of 84.63 ± 2.35%. Intranasal administration achieved a high brain accumulation of 3.84 ± 0.28 μg/mL, drug targeting index (DTI) of 7.24 and drug targeting percentage (DTP) of 86.2%. The innovative integration of La-mediated cell penetration with intranasal nose-to-brain delivery provides a promising translational platform for improving DTB delivery to GBM.