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The aim of this study was to target a naturally chemotherapeutic agent: ferulic acid to the liver using a biocompatible and an in vivo stable carrier. Accordingly, chitosan as a biopolymer was modified using a hydrophobic moiety and valeric acid in order to increase its in vivo stability. The structure of the newly synthesized product was confirmed using FT-IR and NMR techniques together with the ninhydrin assay. Ferulic acid was conjugated to the modified nanoparticles that were further characterized for particle size, PDI and zeta potential and subjected to ex vivo stability study in serum and cytotoxicity studies in HepG2 cell lines. Furthermore, the nanoparticles were surface-decorated with glycyrrhizin for active liver targeting. The in vivo biodistribution was experimented using radiolabeling assay where the liver scored the highest accumulation of the glycyrrhizin containing nanoparticles after 6 h reaching a value of 13.34% ID/g of the total injected dose of labeled drug compared to drug solution and glycyrrhizin free nanoparticles where the accumulation percent did not exceed 4.19% ID/g and 4.26% ID/g, respectively. As a conclusion, the conducted physico-chemical and biological investigations suggested that the proposed selected system can be efficiently utilized as a successful platform for targeting a natural chemotherapeutic agent viz. ferulic acid to the liver.Valerate-conjugated chitosan nanoparticles surface decorated with glycyrrhizin augments the cytotoxicity of ferulic acid and successfully targets it to the liver.