Development and in vitro evaluation of chitosan nanoparticles encapsulating <i>Phoenix dactylifera</i> L. (Ajwah) seed extract with supporting in silico molecular docking analysis

Abstract This research describes the engineering of chitosan nanoparticles (CS NPs) via ionic gelation to encapsulate Ajwah seed extract (ASE), repurposing a plant waste product for its documented antioxidant and anticancer potential. Physicochemical analysis confirmed the formation of stable nanoparticles with hydrodynamic diameters between 152.3 and 254.93 nm and a smaller primary core size (≈68.87 nm) observed via transmission electron microscopy. The CS−ASE2 formulation (1:5 w/w) was deemed optimal due to its superior encapsulation efficiency and drug loading. Functional evaluation revealed a 1.2‐fold enhancement in the extract's antioxidant activity upon encapsulation. Release kinetics displayed a non‐Fickian profile, indicating a sustained and controlled delivery of ASE. The chitosan nanoparticles encapsulating Ajwah seed extract (CS/ASE NPs) also a demonstrates notable selective toxicity on cancer cell lines showing IC50 values on human colorectal cancer (HCT‐116)—233 μg/mL, breast cancer (MCF‐7)—351 μg/mL, and prostate cancer (PC‐3) cell lines—478 μg/mL. In contrast, their effect on normal human cells (HFB‐4) was weaker (IC 50 = 749.4 μg/mL), indicating selectivity toward cancer cells. These findings suggest that CS/ASE NPs have strong potential as an alternative anticancer treatment.