pH- responsive chitosan nanoparticles loaded with lapatinib trigger apoptosis and inhibit P-gp activity in HCT116 and SW480 colorectal cancer cells

This research produces Lapatinib-encapsulated Chitosan Nanoparticles (LPTB-CS-NPs) through ionic gelation to improve colorectal cancer treatment. Optimized LPTB-CS-NPs-8 displayed a particle size of 192.27 ± 8.5 nm, a PDI of 0.204 ± 0.07, a zeta potential of +17.3 ± 6.3 mV, and an encapsulation efficiency of 75.8 ± 2.2 %. In vitro release exhibited pH sensitivity (89.3 ± 5.4 % at pH 5.5 compared to 75.6 ± 5.0 % at pH 7.4 over 72 h; Higuchi model, R² = 0.982), supporting delivery targeted to tumors. LPTB-CS-NPs improved uptake in HCT116 and SW480 cells (90.7 ± 5.4 % and 65.4 ± 8.8 %, respectively), decreased viability (IC₅₀: 12.56 ± 2.42 µg/mL for HCT116; 34.12 ± 4.7 µg/mL for SW480), and hindered migration (∼80 % in HCT116). Induction of apoptosis (50 % in HCT116; 40 % in SW480) was linked to DNA fragmentation (∼32 % SW480; ∼22 % HCT116), increased ROS (∼4500 a.u. in HCT116), and inhibition of EGFR/HER2 pathways. P-gp function reduced by 33–35 %, addressing multidrug resistance. These findings establish LPTB-CS-NPs as a strong foundation for CRC treatment, integrating targeted delivery, tumor-specific release, and reversal of resistance, setting the stage for in vivo research and clinical application.