Development and in vitro evaluation of chitosan nanoparticles encapsulating Phoenix dactylifera 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.